Large Artery Atherosclerotic Occlusive Disease

PubMed Central

Cole, John W.

2017-01-01

ABSTRACT Purpose of Review: Extracranial or intracranial large artery atherosclerosis is often identified as a potential etiologic cause for ischemic stroke and transient ischemic attack. Given the high prevalence of large artery atherosclerosis in the general population, determining whether an identified atherosclerotic lesion is truly the cause of a patient’s symptomatology can be difficult. In all cases, optimally treating each patient to minimize future stroke risk is paramount. Extracranial or intracranial large artery atherosclerosis can be broadly compartmentalized into four distinct clinical scenarios based upon the individual patient’s history, examination, and anatomic imaging findings: asymptomatic and symptomatic extracranial carotid stenosis, intracranial atherosclerosis, and extracranial vertebral artery atherosclerotic disease. This review provides a framework for clinicians evaluating and treating such patients. Recent Findings: Intensive medical therapy achieves low rates of stroke and death in asymptomatic carotid stenosis. Evidence indicates that patients with severe symptomatic carotid stenosis should undergo carotid revascularization sooner rather than later and that the risk of stroke or death is lower using carotid endarterectomy than with carotid stenting. Specific to stenting, the risk of stroke or death is greatest among older patients and women. Continuous vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy is the mainstay for stroke prevention in the setting of intracranial and vertebral artery origin atherosclerosis. Summary: Lifelong vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy are the key elements to reduce future stroke risk in the setting of large artery atherosclerosis. When considering a revascularization procedure for carotid stenosis, patient demographics, comorbidities, and the periprocedural risks of stroke and

Intra-plaque production of platelet-activating factor correlates with neoangiogenesis in human carotid atherosclerotic lesions.

PubMed

Lupia, Enrico; Pucci, Angela; Peasso, Paolo; Merlo, Maurizio; Baron, Paolo; Zanini, Cristina; Del Sorbo, Lorenzo; Rizea-Savu, Simona; Silvestro, Luigi; Forni, Marco; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

2003-09-01

Platelet-activating factor (PAF) is a phospholipid mediator synthesized by activated inflammatory and endothelial cells. Recently PAF has been shown to contribute to neoangiogenesis in several experimental models. Here we evaluated the presence of PAF and its potential role in neovascularization within human atherosclerotic plaques. The amount of PAF extracted from 18 carotid plaques (266.65+/-40.07 pg/100 mg dry tissue; mean +/- SE) was significantly higher than that extracted from 18 normal arterial specimens (6 from carotid artery and 12 from aorta) (4.72+/-2.31 pg/100 mg dry tissue; mean +/- SE). The levels of PAF significantly correlated with the infiltration of CD68-positive monocytes and the extent of neovascularization, detected as von Willebrand Factor-positive cells. The amount of PAF also correlated with the area occupied by TNF-alpha-expressing cells. The absence of enhanced level of PAF in the circulation of atherosclerotic patients suggests a local production of this mediator within the plaque. The lipid extracts of atherosclerotic plaques containing high levels of PAF-bioactivity, but not those of control arteries, were angiogenic in a murine Matrigel model. WEB 2170, a specific PAF receptor antagonist, significantly prevented angiogenesis induced by the lipid extracts of atherosclerotic plaques. Our results indicate a local production of PAF within the atherosclerotic plaques and suggest that it may contribute to intra-plaque neoangiogenesis.

Ghrelin inhibits atherosclerotic plaque angiogenesis and promotes plaque stability in a rabbit atherosclerotic model.

PubMed

Wang, Li; Chen, Qingwei; Ke, Dazhi; Li, Guiqiong

2017-04-01

Intraplaque angiogenesis associates with the instability of atherosclerotic plaques. In the present study, we investigated the effects of ghrelin on intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis. The rabbits were randomly divided into three groups, namely, the control group, atherosclerotic model group, and ghrelin-treated group, with treatments lasting for 4 weeks. We found that the thickness ratio of the intima to media in rabbits of the ghrelin-treated group was significantly lower than that in rabbits of the atherosclerotic model group. The number of neovessels and the levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) decreased dramatically in rabbits of the ghrelin-treated group compared to those of the atherosclerotic model group. Ghrelin significantly decreased the plaque content of macrophages, matrix metalloproteinase (MMP)-2, and MMP-9, in a rabbit model of atherosclerosis. In addition, the level of the pro-inflammatory factor monocyte chemoattractant protein (MCP)-1 was significantly lower in rabbits of the ghrelin-treated group than in rabbits of the atherosclerotic model group. In summary, ghrelin can inhibit intraplaque angiogenesis and promote plaque stability by down-regulating VEGF and VEGFR2 expression, inhibiting the plaque content of macrophages, and reducing MCP-1 expression at an advanced stage of atherosclerosis in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

Common genetic risk factors for coronary artery disease: new opportunities for prevention?

PubMed

Hamrefors, Viktor

2017-05-01

Atherosclerotic cardiovascular disease (CVD) is a leading cause of mortality and morbidity worldwide, with coronary artery disease (CAD) being the single leading cause of death. Better control of risk factors, enhanced diagnostic techniques and improved medical therapies have all substantially decreased the mortality of CAD in developed countries. However, CAD and other forms of atherosclerotic CVD are projected to remain the leading cause of death by 2030 and we face a number of challenges if the outcomes of CAD are to be further improved. The fact that a substantial fraction of high-risk subjects do not reach treatment goals for important risk factors is one of these challenges. At the same time, there is also a non-negotiable fraction of 'concealed' high-risk subjects who are not detected by current risk algorithms and diagnostic modalities. In recent years, we have started to rapidly increase our knowledge of the framework of common genetics underlying CAD and atherosclerotic CVD in the population. In conjunction with modern diagnostic and therapeutic options, this new genetic knowledge may provide a valuable tool for further improvements in prevention. This review summarizes the recent findings from the search for common genetic risk factors for CAD. Furthermore, the author discusses how such recent findings could potentially be used in a number of clinical applications within CAD prevention, including in clinical risk stratification, in prediction of drug treatment response and in the search for targets for novel preventive therapies. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress.

PubMed

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-11-18

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis -induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research.

Imaging of oxidation-specific epitopes with targeted nanoparticles to detect high-risk atherosclerotic lesions: Progress and future directions

PubMed Central

Briley-Saebo, Karen; Yeang, Calvin; Witztum, Joseph L.; Tsimikas, Sotirios

2014-01-01

Oxidation-specific epitopes (OSE) within developing atherosclerotic lesions are key antigens that drive innate and adaptive immune responses in atherosclerosis, leading to chronic inflammation. Oxidized phospholipids and malondialdehyde-lysine epitopes are well-characterized OSE present in human atherosclerotic lesions, particularly in pathologically defined vulnerable plaques. Using murine and human OSE-specific antibodies as targeting agents, we have developed radionuclide and magnetic resonance based nanoparticles, containing gadolinium, manganese or lipid-coated ultrasmall superparamagnetic iron oxide, to noninvasively image OSE within experimental atherosclerotic lesions. These methods quantitate plaque burden, allow detection of lesion progression and regression, plaque stabilization, and accumulation of OSE within macrophage-rich areas of the artery wall, suggesting they detect the most active lesions. Future studies will focus on using “natural” antibodies, lipopeptides and mimotopes for imaging applications. These approaches should enhance the clinical translation of this technique to image, monitor, evaluate efficacy of novel therapeutic agents and guide optimal therapy of high-risk atherosclerotic lesions. PMID:25297940

Atherosclerotic Plaque in Patients with Zero Calcium Score at Coronary Computed Tomography Angiography

PubMed Central

Gabriel, Fabíola Santos; Gonçalves, Luiz Flávio Galvão; de Melo, Enaldo Vieira; Sousa, Antônio Carlos Sobral; Pinto, Ibraim Masciarelli Francisco; Santana, Sara Melo Macedo; de Matos, Carlos José Oliveira; Souto, Maria Júlia Silveira; Conceição, Flávio Mateus do Sacramento; Oliveira, Joselina Luzia Menezes

2018-01-01

Background In view of the high mortality for cardiovascular diseases, it has become necessary to stratify the main risk factors and to choose the correct diagnostic modality. Studies have demonstrated that a zero calcium score (CS) is characteristic of a low risk for cardiovascular events. However, the prevalence of individuals with coronary atherosclerotic plaques and zero CS is conflicting in the specialized literature. Objective To evaluate the frequency of patients with coronary atherosclerotic plaques, their degree of obstruction and associated factors in patients with zero CS and indication for coronary computed tomography angiography (CCTA). Methods This is a cross-sectional, prospective study with 367 volunteers with zero CS at CCTA in four diagnostic imaging centers in the period from 2011 to 2016. A significance level of 5% and 95% confidence interval were adopted. Results The frequency of atherosclerotic plaque in the coronary arteries in 367 patients with zero CS was 9.3% (34 individuals). In this subgroup, mean age was 52 ± 10 years, 18 (52.9%) were women and 16 (47%) had significant coronary obstructions (> 50%), with involvement of two or more segments in 4 (25%) patients. The frequency of non-obese individuals (90.6% vs 73.9%, p = 0.037) and alcohol drinkers (55.9% vs 34.8%, p = 0.015) was significantly higher in patients with atherosclerotic plaques, with an odds ratio of 3.4 for each of this variable. Conclusions The frequency of atherosclerotic plaque with zero CS was relatively high, indicating that the absence of calcification does not exclude the presence of plaques, many of which obstructive, especially in non-obese subjects and alcohol drinkers. PMID:29723329

Atherosclerotic Plaque in Patients with Zero Calcium Score at Coronary Computed Tomography Angiography.

PubMed

Gabriel, Fabíola Santos; Gonçalves, Luiz Flávio Galvão; Melo, Enaldo Vieira de; Sousa, Antônio Carlos Sobral; Pinto, Ibraim Masciarelli Francisco; Santana, Sara Melo Macedo; Matos, Carlos José Oliveira de; Souto, Maria Júlia Silveira; Conceição, Flávio Mateus do Sacramento; Oliveira, Joselina Luzia Menezes

2018-05-03

In view of the high mortality for cardiovascular diseases, it has become necessary to stratify the main risk factors and to choose the correct diagnostic modality. Studies have demonstrated that a zero calcium score (CS) is characteristic of a low risk for cardiovascular events. However, the prevalence of individuals with coronary atherosclerotic plaques and zero CS is conflicting in the specialized literature. To evaluate the frequency of patients with coronary atherosclerotic plaques, their degree of obstruction and associated factors in patients with zero CS and indication for coronary computed tomography angiography (CCTA). This is a cross-sectional, prospective study with 367 volunteers with zero CS at CCTA in four diagnostic imaging centers in the period from 2011 to 2016. A significance level of 5% and 95% confidence interval were adopted. The frequency of atherosclerotic plaque in the coronary arteries in 367 patients with zero CS was 9.3% (34 individuals). In this subgroup, mean age was 52 ± 10 years, 18 (52.9%) were women and 16 (47%) had significant coronary obstructions (> 50%), with involvement of two or more segments in 4 (25%) patients. The frequency of non-obese individuals (90.6% vs 73.9%, p = 0.037) and alcohol drinkers (55.9% vs 34.8%, p = 0.015) was significantly higher in patients with atherosclerotic plaques, with an odds ratio of 3.4 for each of this variable. The frequency of atherosclerotic plaque with zero CS was relatively high, indicating that the absence of calcification does not exclude the presence of plaques, many of which obstructive, especially in non-obese subjects and alcohol drinkers.

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress

PubMed Central

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-01-01

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis-induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research. PMID:29156574

Renal function during pregnancy may predict risk of future hospitalization due to atherosclerotic-related morbidity.

PubMed

Wolak, Talya; Shoham-Vardi, Ilana; Sergienko, Ruslan; Sheiner, Eyal

2016-02-01

This study aims to examine whether renal function during pregnancy can serve as a surrogate marker for the risk of developing atherosclerotic-related morbidity. A case-control study, including women who gave birth at a tertiary referral medical centre during 2000-2012. This population was divided into cases of women who were subsequently hospitalized for atherosclerotic morbidity during the study period and age-matched controls. From the study population, we retrieved two groups: the creatinine (Cr) group: women who had at least one Cr measurement (4945 women) and the urea group: women who had at least one urea measurement (4932 women) during their pregnancies. In the Cr and urea group, there were 572 and 571 cases and 4373 and 4361 controls, respectively. The mean follow-up period in the Cr and urea group was 61.7 ± 37.0 and 57.3 ± 36.0 months, respectively. Cox proportional hazards models (controlling for confounders: gestational hypertension, gestational diabetes, obesity, maternal age, creatinine level (for urea), and gestational week) were used to estimate the adjusted hazard ratios (HR) for hospitalizations. A significant association was documented between renal function during pregnancy and long-term atherosclerotic morbidity. Multivariate analysis, showed that Cr at pregnancy index of ≥89 μmol/L was associated with a significant increased risk for hospitalization due to cardiovascular (CVS) events (adjusted HR = 2.91 CI 1.37-6.19 P = 0.005) and urea level ≤7 mmol/L was independently associated with reduced prevalence of CVS hospitalization (adjusted HR = 0.62 CI 0.57-0.86 P = 0.001). Renal function abnormality during pregnancy may reveal occult predisposition to atherosclerotic morbidity years after childbirth. © 2015 Asian Pacific Society of Nephrology.

Cardiovascular risk factors and disease in women.

PubMed

Gill, Sharon K

2015-05-01

Coronary artery disease and stroke predominantly affect older women as opposed to younger women, but the risk factors that contribute to atherosclerotic cardiovascular disease risk often start in young women. Young women with polycystic ovary syndrome (PCOS), with migraine, and who use oral contraceptive pills (OCPs) have short-term increases in thrombotic complications that can result in coronary events or stroke. Attention should be focused on risk reduction in women of all ages. Screening for and discussing diabetes, hypertension, obesity, smoking, migraine, PCOS, and pregnancy complication history and discussing the pros and cons of hormone and statin medications are part of reducing cardiovascular risk for women. Published by Elsevier Inc.

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events

PubMed Central

Hoefer, Imo E.; Eijkemans, Marinus J. C.; Asselbergs, Folkert W.; Anderson, Todd J.; Britton, Annie R.; Dekker, Jacqueline M.; Engström, Gunnar; Evans, Greg W.; de Graaf, Jacqueline; Grobbee, Diederick E.; Hedblad, Bo; Holewijn, Suzanne; Ikeda, Ai; Kitagawa, Kazuo; Kitamura, Akihiko; de Kleijn, Dominique P. V.; Lonn, Eva M.; Lorenz, Matthias W.; Mathiesen, Ellisiv B.; Nijpels, Giel; Okazaki, Shuhei; O’Leary, Daniel H.; Pasterkamp, Gerard; Peters, Sanne A. E.; Polak, Joseph F.; Price, Jacqueline F.; Robertson, Christine; Rembold, Christopher M.; Rosvall, Maria; Rundek, Tatjana; Salonen, Jukka T.; Sitzer, Matthias; Stehouwer, Coen D. A.; Bots, Michiel L.; den Ruijter, Hester M.

2015-01-01

Background Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. Methods We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. Results Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. Conclusion The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention. PMID:26134404

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.

PubMed

Gijsberts, Crystel M; Groenewegen, Karlijn A; Hoefer, Imo E; Eijkemans, Marinus J C; Asselbergs, Folkert W; Anderson, Todd J; Britton, Annie R; Dekker, Jacqueline M; Engström, Gunnar; Evans, Greg W; de Graaf, Jacqueline; Grobbee, Diederick E; Hedblad, Bo; Holewijn, Suzanne; Ikeda, Ai; Kitagawa, Kazuo; Kitamura, Akihiko; de Kleijn, Dominique P V; Lonn, Eva M; Lorenz, Matthias W; Mathiesen, Ellisiv B; Nijpels, Giel; Okazaki, Shuhei; O'Leary, Daniel H; Pasterkamp, Gerard; Peters, Sanne A E; Polak, Joseph F; Price, Jacqueline F; Robertson, Christine; Rembold, Christopher M; Rosvall, Maria; Rundek, Tatjana; Salonen, Jukka T; Sitzer, Matthias; Stehouwer, Coen D A; Bots, Michiel L; den Ruijter, Hester M

2015-01-01

Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

Detection of high-risk atherosclerotic lesions by time-resolved fluorescence spectroscopy based on the Laguerre deconvolution technique

NASA Astrophysics Data System (ADS)

Jo, J. A.; Fang, Q.; Papaioannou, T.; Qiao, J. H.; Fishbein, M. C.; Beseth, B.; Dorafshar, A. H.; Reil, T.; Baker, D.; Freischlag, J.; Marcu, L.

2006-02-01

This study introduces new methods of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data analysis for tissue characterization. These analytical methods were applied for the detection of atherosclerotic vulnerable plaques. Upon pulsed nitrogen laser (337 nm, 1 ns) excitation, TR-LIFS measurements were obtained from carotid atherosclerotic plaque specimens (57 endarteroctomy patients) at 492 distinct areas. The emission was both spectrally- (360-600 nm range at 5 nm interval) and temporally- (0.3 ns resolution) resolved using a prototype clinically compatible fiber-optic catheter TR-LIFS apparatus. The TR-LIFS measurements were subsequently analyzed using a standard multiexponential deconvolution and a recently introduced Laguerre deconvolution technique. Based on their histopathology, the lesions were classified as early (thin intima), fibrotic (collagen-rich intima), and high-risk (thin cap over necrotic core and/or inflamed intima). Stepwise linear discriminant analysis (SLDA) was applied for lesion classification. Normalized spectral intensity values and Laguerre expansion coefficients (LEC) at discrete emission wavelengths (390, 450, 500 and 550 nm) were used as features for classification. The Laguerre based SLDA classifier provided discrimination of high-risk lesions with high sensitivity (SE>81%) and specificity (SP>95%). Based on these findings, we believe that TR-LIFS information derived from the Laguerre expansion coefficients can provide a valuable additional dimension for the diagnosis of high-risk vulnerable atherosclerotic plaques.

Atherosclerosis and clonal hematopoyesis: A new risk factor.

PubMed

Páramo Fernández, José A

Recent research has revealed that clonal hematopoyesis of indeterminate potential (CHIP) characterized by the acquisition of somatic mutations in hematopoietic stem cells, is not only a common age-related disorder and a premalignant condition, but it is also associated with the development of atherosclerotic vascular diseases. Mutations in DNMT3A, TET2 and ASXL1 were each individually associated with coronary heart disease, stroke and coronary calcification. Therefore, CHIP emerges as a new risk factor for atherosclerotic vascular pathologies and its detection may be relevant as a new therapeutic target in order to modify the natural course of the disease. Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Healthy Lifestyle and Risk of Kidney Disease Progression, Atherosclerotic Events, and Death in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

PubMed Central

Ricardo, Ana C.; Anderson, Cheryl A.; Yang, Wei; Zhang, Xiaoming; Fischer, Michael J.; Dember, Laura M.; Fink, Jeffrey C.; Frydrych, Anne; Jensvold, Nancy; Lustigova, Eva; Nessel, Lisa C.; Porter, Anna C.; Rahman, Mahboob; Wright, Julie A.; Daviglus, Martha L.; Lash, James P.

2014-01-01

Background In general populations, healthy lifestyle is associated with fewer adverse outcomes. We estimated the degree to which adherence to a healthy lifestyle decreases the risk of renal and cardiovascular events among adults with chronic kidney disease (CKD). Study Design Prospective cohort. Setting & Participants 3006 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictors Four lifestyle factors (regular physical activity, body mass index [BMI] 20–<25 kg/m2, nonsmoking, and “healthy diet”), individually and in combination. Outcomes CKD progression (50% decrease in estimated glomerular filtration rate or end-stage renal disease), atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease), and all-cause mortality. Measurements Multivariable-adjusted Cox proportional hazards. Results During median follow-up of 4 years, we observed 726 CKD progression events, 353 atherosclerotic events, and 437 deaths. BMI ≥ 25 kg/m2 and nonsmoking were associated with reduced risk of CKD progression (HRs of 0.75 [95% CI, 0.58–0.97] and 0.61 [95% CI, 0.45–0.82] for BMIs of 25–<30 and ≥30, respectively, vs. 20–<25 kg/m2; HR for nonsmoking of 0.68 [95% CI, 0.55–0.84] compared to current smoker reference group) and reduced risk of atherosclerotic events (HRs of 0.67 [95% CI, 0.46–0.96] for BMI 25–<30 vs. 20–<25 kg/m2 and 0.55 [95% CI, 0.40–0.75] vs. current smoker). Factors associated with reduced all-cause mortality were regular physical activity (HR, 0.64 [95% CI, 0.52–0.79] vs. inactive), BMI ≥30 kg/m2 (HR, 0.64 [95% CI, 0.43–0.96] vs. 20–<25 kg/m2) and nonsmoking (HR, 0.45 [95% CI, 0.34–0.60] vs. current smoker). BMI <20 kg/m2 was associated with increased all-cause mortality risk (HR, 2.11 [95% CI, 1.13–3.93] vs. 20–25 kg/m2). Adherence to all four lifestyle factors was associated with 68% lower risk of all-cause mortality compared to adherence to no lifestyle factors (HR, 0.32; 95

Is triglyceride/HDL ratio a reliable screening test for assessment of atherosclerotic risk in patients with chronic inflammatory disease?

PubMed

Keles, Nursen; Aksu, Feyza; Aciksari, Gonul; Yilmaz, Yusuf; Demircioglu, Kenan; Kostek, Osman; Cekin, Muhammed Esad; Kalcik, Macit; Caliskan, Mustafa

2016-01-01

The term chronic inflammatory disease (CID) refers to a category of inflammatory diseases that includes Ankylosing spondylitis (AS) and familial Mediterranean fever (FMF). The incidence of adverse cardiovascular events is greater among patients with CID, though they may not have conventional atherosclerotic risk factors. Endothelial dysfunction is one of the underlying fundamental mechanisms that trigger development of atherosclerotic alterations in arteries, and flow-mediated dilatation (FMD) is a noninvasive method to determine endothelial dysfunction. Recent studies have shown a relationship between high triglyceride high-density lipoprotein cholesterol (TG/HDL-C) ratio and coronary atherosclerosis. Many studies have demonstrated that patients with CID have lower FMD values compared to healthy population, indicating endothelial dysfunction. However TG/HDL ratio and its relationship to FMD in patients with CID has not been investigated. The present study investigated whether TG/HDL ratio in CID patients differs from that of healthy population, and its relationship to FMD in patients with CID. A total of 58 patients with CID and a group of 58 healthy volunteer individuals were enrolled in the study. FMD measurements were taken with high resolution ultrasound (US), and TG/HDL ratios were calculated. Patients with CID had significantly higher TG/HDL-C ratio (2.5 [2.2-2.8] vs 2.3 [2.1-2.5]; p=0.03) and lower FMD values (5.2 [4.2-6.3] vs 6.7 [6.3-9.7]; p<0.001), compared to healthy group, and a negative correlation was found between FMD levels and TG/HDL ratio of the study population. Higher TG/HDL ratio and lower FMD values found in CID patients may reflect increased atherosclerotic risk.

Cardiovascular disease risk factors: a childhood perspective.

PubMed

Praveen, Pradeep A; Roy, Ambuj; Prabhakaran, Dorairaj

2013-03-01

Atherosclerotic cardiovascular disease (CVD) is one of the leading causes of death and disability worldwide including in developing countries like India. Indians are known to be predisposed to CVD, which occur almost a decade earlier in them. Though these diseases manifest in the middle age and beyond, it is now clear that the roots of CVD lie in childhood and adolescence. Many of the conventional risk factors of CVD such as high blood pressure, dyslipidemia, tobacco use, unhealthy diet and obesity have their beginnings in childhood and then track overtime. It is thus important to screen and identify these risk factors early and treat them to prevent onset of CVD. Similarly community based strategies to prevent onset of these risk factors is imperative to tackle this burgeoning public health crisis especially in countries like ours with limited resources.

Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus.

PubMed

Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

2013-04-01

Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls. The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured. Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60 vs. 345 ± 64 U. Carr., P<0.05). A multiple linear regression analysis revealed that systolic BP (β=0.26, P<0.05) and high-density lipoprotein cholesterol (HDL-C: β= -0.30, P<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (β = 0.44, P<0.05) and HDL-C (β = -0.36, P<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (β = -0.36, P=0.06) in males with T2DM. The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis.

Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus

PubMed Central

Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

2013-01-01

Background & objectives: Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls. Methods: The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured. Results: Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60 vs. 345 ± 64 U. Carr., P<0.05). A multiple linear regression analysis revealed that systolic BP (β=0.26, P<0.05) and high-density lipoprotein cholesterol (HDL-C: β= -0.30, P<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (β = 0.44, P<0.05) and HDL-C (β = -0.36, P<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (β = -0.36, P=0.06) in males with T2DM. Interpretation & conclusions: The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis. PMID:23703342

Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events.

PubMed

Go, Alan S; Hsu, Chi-Yuan; Yang, Jingrong; Tan, Thida C; Zheng, Sijie; Ordonez, Juan D; Liu, Kathleen D

2018-06-07

AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge. We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records. Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12). AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge. Copyright © 2018 by the American Society of Nephrology.

The Veterans Affairs Cardiac Risk Score: Recalibrating the Atherosclerotic Cardiovascular Disease Score for Applied Use.

PubMed

Sussman, Jeremy B; Wiitala, Wyndy L; Zawistowski, Matthew; Hofer, Timothy P; Bentley, Douglas; Hayward, Rodney A

2017-09-01

Accurately estimating cardiovascular risk is fundamental to good decision-making in cardiovascular disease (CVD) prevention, but risk scores developed in one population often perform poorly in dissimilar populations. We sought to examine whether a large integrated health system can use their electronic health data to better predict individual patients' risk of developing CVD. We created a cohort using all patients ages 45-80 who used Department of Veterans Affairs (VA) ambulatory care services in 2006 with no history of CVD, heart failure, or loop diuretics. Our outcome variable was new-onset CVD in 2007-2011. We then developed a series of recalibrated scores, including a fully refit "VA Risk Score-CVD (VARS-CVD)." We tested the different scores using standard measures of prediction quality. For the 1,512,092 patients in the study, the Atherosclerotic cardiovascular disease risk score had similar discrimination as the VARS-CVD (c-statistic of 0.66 in men and 0.73 in women), but the Atherosclerotic cardiovascular disease model had poor calibration, predicting 63% more events than observed. Calibration was excellent in the fully recalibrated VARS-CVD tool, but simpler techniques tested proved less reliable. We found that local electronic health record data can be used to estimate CVD better than an established risk score based on research populations. Recalibration improved estimates dramatically, and the type of recalibration was important. Such tools can also easily be integrated into health system's electronic health record and can be more readily updated.

Is triglyceride/HDL ratio a reliable screening test for assessment of atherosclerotic risk in patients with chronic inflammatory disease?

PubMed Central

Keles, Nursen; Aksu, Feyza; Aciksari, Gonul; Yilmaz, Yusuf; Demircioglu, Kenan; Kostek, Osman; Cekin, Muhammed Esad; Kalcik, Macit; Caliskan, Mustafa

2016-01-01

OBJECTIVE: The term chronic inflammatory disease (CID) refers to a category of inflammatory diseases that includes Ankylosing spondylitis (AS) and familial Mediterranean fever (FMF). The incidence of adverse cardiovascular events is greater among patients with CID, though they may not have conventional atherosclerotic risk factors. Endothelial dysfunction is one of the underlying fundamental mechanisms that trigger development of atherosclerotic alterations in arteries, and flow-mediated dilatation (FMD) is a noninvasive method to determine endothelial dysfunction. Recent studies have shown a relationship between high triglyceride high-density lipoprotein cholesterol (TG/HDL-C) ratio and coronary atherosclerosis. Many studies have demonstrated that patients with CID have lower FMD values compared to healthy population, indicating endothelial dysfunction. However TG/HDL ratio and its relationship to FMD in patients with CID has not been investigated. The present study investigated whether TG/HDL ratio in CID patients differs from that of healthy population, and its relationship to FMD in patients with CID. METHODS: A total of 58 patients with CID and a group of 58 healthy volunteer individuals were enrolled in the study. FMD measurements were taken with high resolution ultrasound (US), and TG/HDL ratios were calculated. RESULTS: Patients with CID had significantly higher TG/HDL-C ratio (2.5 [2.2–2.8] vs 2.3 [2.1–2.5]; p=0.03) and lower FMD values (5.2 [4.2–6.3] vs 6.7 [6.3–9.7]; p<0.001), compared to healthy group, and a negative correlation was found between FMD levels and TG/HDL ratio of the study population. CONCLUSION: Higher TG/HDL ratio and lower FMD values found in CID patients may reflect increased atherosclerotic risk. PMID:28058384

Spatial distribution of osteoblast-specific transcription factor Cbfa1 and bone formation in atherosclerotic arteries.

PubMed

Bobryshev, Yuri V; Killingsworth, Murray C; Lord, Reginald S A

2008-08-01

The mechanisms of ectopic bone formation in arteries are poorly understood. Osteoblasts might originate either from stem cells that penetrate atherosclerotic plaques from the blood stream or from pluripotent mesenchymal cells that have remained in the arterial wall from embryonic stages of the development. We have examined the frequency of the expression and spatial distribution of osteoblast-specific factor-2/core binding factor-1 (Osf2/Cbfa1) in carotid and coronary arteries. Cbfa1-expressing cells were rarely observed but were found in all tissue specimens in the deep portions of atherosclerotic plaques under the necrotic cores. The deep portions of atherosclerotic plaques under the necrotic cores were characterized by the lack of capillaries of neovascularization. In contrast, plaque shoulders, which were enriched by plexuses of neovascularization, lacked Cbfa1-expressing cells. No bone formation was found in any of the 21 carotid plaques examined and ectopic bone was observed in only two of 12 coronary plaques. We speculate that the sparse invasion of sprouts of neovascularization into areas underlying the necrotic cores, where Cbfa1-expressing cells reside, might explain the rarity of events of ectopic bone formation in the arterial wall. This study has also revealed that Cbfa1-expressing cells contain alpha-smooth muscle actin and myofilaments, indicating their relationship with arterial smooth muscle cells.

Exercise training protects against atherosclerotic risk factors through vascular NADPH oxidase, extracellular signal-regulated kinase 1/2 and stress-activated protein kinase/c-Jun N-terminal kinase downregulation in obese rats.

PubMed

Touati, Sabeur; Montezano, Augusto C I; Meziri, Fayçal; Riva, Catherine; Touyz, Rhian M; Laurant, Pascal

2015-02-01

Exercise training reverses atherosclerotic risk factors associated with metabolic syndrome and obesity. The aim of the present study was to determine the molecular anti-inflammatory, anti-oxidative and anti-atherogenic effects in aorta from rats with high-fat diet-induced obesity. Male Sprague-Dawley rats were placed on a high-fat (HFD) or control (CD) diet for 12 weeks. The HFD rats were then divided into four groups: (i) sedentary HFD-fed rats (HFD-S); (ii) exercise trained (motor treadmill 5 days/week, 60 min/day, 12 weeks) HFD-fed rats (HFD-Ex); (iii) modified diet (HFD to CD) sedentary rats (HF/CD-S); and (iv) an exercise-trained modified diet group (HF/CD-Ex). Tissue levels of NADPH oxidase (activity and expression), NADPH oxidase (Nox) 1, Nox2, Nox4, p47(phox) , superoxide dismutase (SOD)-1, angiotensin AT1 and AT2 receptors, phosphorylated mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase (ERK) 1/2, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the aorta. Plasma cytokines (tumour necrosis factor (TNF)-α and interleukin (IL)-6) levels were also measured. Obesity was accompanied by increases in NADPH oxidase activity, p47(phox) translocation, Nox4 and VCAM-1 protein expression, MAPK (ERK1/2, SAPK/JNK) phosphorylation and plasma TNF-α and IL-6 levels. Exercise training and switching from the HFD to CD reversed almost all these molecular changes. In addition, training increased aortic SOD-1 protein expression and decreased ERK1/2 phosphorylation. These findings suggest that protective effects of exercise training on atherosclerotic risk factors induced by obesity are associated with downregulation of NADPH oxidase, ERK1/2 and SAPK/JNK activity and increased SOD-1 expression. © 2014 Wiley Publishing Asia Pty Ltd.

Long-term patency of superficial temporal artery to middle cerebral artery bypass for cerebral atherosclerotic disease: factors determining the bypass patent.

PubMed

Matano, Fumihiro; Murai, Yasuo; Tateyama, Kojiro; Tamaki, Tomonori; Mizunari, Takayuki; Matsukawa, Hideoshi; Teramoto, Akira; Morita, Akio

2016-10-01

Long-term patency of superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery for atherosclerotic disease and associated risk factors for loss of patency have rarely been discussed. We retrospectively analyzed long-term patency following STA-MCA bypass and evaluated various demographic and clinical factors to identify the ones predictive of postsurgical loss of patency using records of 84 revascularization procedures (58 patients, 45 males; mean age at surgery 63.6 years, range 31-78 years). Bypass patency was diagnosed based on magnetic resonance angiography or three-dimensional computed tomography. The mean follow-up period was 24.7 months (range 6-63 months). Decreased bypass patency was observed in 4 of 58 patients (6.9 %) who collectively underwent 6 bypasses (7.1 %) of 84. All cases of decreased bypass patency were first detected within 6 months of surgery. Bypass patency was not correlated with age, sex, number of anastomoses, postoperative cerebral infarction, or control of postoperative diabetes mellitus. We found a significant association of bypass patency with hyperperfusion (p = 0.01) and postoperative smoking (p = 0.0036). Furthermore, we found a significant association of hyperperfusion with STA diameter (p < 0.0001), location of anastomosis (p = 0.075), and preoperative cerebral blood flow (p = 0.0399). In our retrospective study, hyperperfusion and smoking after surgery may be risk factors for decreased bypass patency in cerebral atherosclerotic disease patients. Careful monitoring of patency to prevent hyperperfusion and cessation of smoking are recommended, particularly within 6 months of the surgery.

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

PubMed

Hansen, Peter Riis

2018-01-01

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Restenosis after renal artery angioplasty and stenting: Incidence and risk factors

PubMed Central

Corriere, Matthew A.; Edwards, Matthew S.; Pearce, Jeffrey D.; Andrews, Jeanette S.; Geary, Randolph L.; Hansen, Kimberley J.

2010-01-01

Background Management of renal artery stenosis (RAS) with primary renal artery percutaneous angioplasty and stenting (RA-PTAS) is associated with a low risk of periprocedural death and major complications; however, restenosis develops in a subset of patients and repeat intervention may be required. We examined the incidence of restenosis after RA-PTAS and associations with clinical factors. Methods Consecutive patients undergoing RA-PTAS for hemodynamically significant atherosclerotic RAS associated with hypertension or ischemic nephropathy, or both, between October 2003 and September 2007 were identified from a registry. Restenosis was defined using duplex ultrasound (DUS) imaging as a renal artery postintervention peak systolic velocity (PSV) ≥180 cm/s. The incidence and temporal distribution of restenosis was analyzed using survival analysis based on treated kidneys. Associations between clinical factors and recurrent stenosis were examined using proportional hazards regression. Results RA-PTAS was performed on 112 kidneys for atherosclerotic RAS during the study period. Initial postintervention renal artery DUS imaging confirming PSV <180 cm/s in 101 kidneys, which formed the basis of this analysis. Estimated restenosis-free survival was 50% at 12 months and 40% at 18 months. Decreased risk of restenosis was associated with preoperative statin use (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.16–0.74; P = .006) and increased preoperative diastolic blood pressure (DBP; HR, 0.70 per 10-mm Hg increase in preoperative DBP; 95% CI, 0.49–0.99; P = .049). No other factors assessed were associated with restenosis. Conclusion Restenosis occurs in a substantial number of patients treated with RA-PTAS. Preoperative statin medication use and increased preoperative DBP are associated with reduced risk of restenosis. In the absence of contraindications, statins should be considered standard therapy for patients with atherosclerotic renal artery stenosis

Paraoxonase 1: a better atherosclerotic risk predictor than HDL in type 2 diabetes mellitus.

PubMed

Patra, Surajeet Kumar; Singh, Kamna; Singh, Ritu

2013-01-01

Type 2 diabetes mellitus is a state of glycative stress and oxidative stress. Lower level of serum PON 1 has been correlated to higher morbidity and mortality related to cardiovascular complications in type 2 diabetes mellitus. To estimate and compare the serum PON 1 levels in type 2 diabetes mellitus and controls and to predict which one is the better atherosclerotic risk predictor among HDL and PON 1 in T2DM patients. An observational analytical case-control study was conducted with a sample size of 30 in two groups like group I (30 cases of type 2 diabetes mellitus diagnosed by ADA 2010 criteria) and group II (30 age and sex matched controls). Human serum paroxonase 1 levels were measured by ELISA. Both HDL and PON 1 were negatively correlated with the various atherogenic indices (AIP, AC, CRI I, CRI II) but the strength of negative correlation is always greater for PON 1. In multiple linear regression analysis, we found that the regression coefficient (β) is always higher for PON 1 than for HDL while taking the atherogenic indices as outcome variable. PON 1 can be a better predictor than HDL for atherosclerotic risk in type 2 diabetes mellitus. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

The Burden of Hard Atherosclerotic Plaques Does Not Promote Endoleak Development After Endovascular Aortic Aneurysm Repair: A Risk Stratification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petersen, Johannes, E-mail: johannes.petersen@i-med.ac.at; Glodny, Bernhard, E-mail: bernhard.glodny@i-med.ac.at

Purpose: To objectify the influence of the atherosclerotic burden in the proximal landing zone on the development of endoleaks after endovascular abdominal aortic aneurysm repair (EVAR) or thoracic endovascular aneurysm repair (TEVAR) using objective aortic calcium scoring (ACS). Materials and Methods: This retrospective observation study included 267 patients who received an aortic endograft between 1997 and 2010 and for whom preoperative computed tomography (CT) was available to perform ACS using the CT-based V600 method. The mean follow-up period was 2 {+-} 2.3 years. Results: Type I endoleaks persisted in 45 patients (16.9%), type II in 34 (12.7%), type III inmore » 8 (3%), and type IV or V in 3 patients, respectively (1.1% each). ACS in patients with type I endoleaks was not increased: 0.029 {+-} 0.061 ml compared with 0.075 {+-} 0.1349 ml in the rest of the patients, (p > 0.05; Whitney-Mann U-Test). There were significantly better results for the indication 'traumatic aortic rupture' than for the other indications (p < 0.05). In multivariate logistic regression analyses, age was an independent risk factor for the development of type I endoleaks in the thoracic aorta (Wald 9.5; p = 0.002), whereas ACS score was an independent protective factor (Wald 6.9; p = 0.009). In the abdominal aorta, neither age nor ACS influenced the development of endoleaks. Conclusion: Contrary to previous assumptions, TEVAR and EVAR can be carried out without increasing the risk of an endoleak of any type, even if there is a high atherosclerotic 'hard-plaque' burden of the aorta. The results are significantly better for traumatic aortic.« less

Anti-atherosclerotic therapy based on botanicals.

PubMed

Orekhov, Alexander N; Sobenin, Igor A; Korneev, Nikolay V; Kirichenko, Tatyana V; Myasoedova, Veronika A; Melnichenko, Alexandra A; Balcells, Mercedes; Edelman, Elazer R; Bobryshev, Yuri V

2013-04-01

Natural products including botanicals for both therapy of clinical manifestations of atherosclerosis and reduction of atherosclerosis risk factors are topics of recent patents. Only a few recent patents are relevant to the direct antiatherosclerotic therapy leading to regression of atherosclerotic lesions. Earlier, using a cellular model we have developed and patented several anti-atherosclerotic drugs. The AMAR (Atherosclerosis Monitoring and Atherogenicity Reduction) study was designed to estimate the effect of two-year treatment with time-released garlic-based drug Allicor on the progression of carotid atherosclerosis in 196 asymptomatic men aged 40-74 in double-blinded placebo-controlled randomized clinical study. The primary outcome was the rate of atherosclerosis progression, measured by high-resolution B-mode ultrasonography as the increase in carotid intima-media thickness (IMT) of the far wall of common carotid arteries. The mean rate of IMT changes in Allicor-treated group (-0.022±0.007 mm per year) was significantly different (P = 0.002) from the placebo group in which there was a moderate progression of 0.015±0.008 mm at the overall mean baseline IMT of 0.931±0.009 mm. A significant correlation was found between the changes in blood serum atherogenicity (the ability of serum to induce cholesterol accumulation in cultured cells) during the study and the changes in intima-media thickness of common carotid arteries (r = 0.144, P = 0.045). Thus, the results of AMAR study demonstrate that long-term treatment with Allicor has a direct anti-atherosclerotic effect on carotid atherosclerosis and this effect is likely to be due to serum atherogenicity inhibition. The beneficial effects of other botanicals including Inflaminat (calendula, elder and violet), phytoestrogen- rich Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) on atherosclerosis have also been revealed in clinical studies

Primary Prevention of Atherosclerotic Cardiovascular Disease in Women

PubMed Central

McKibben, Rebeccah A.; Al Rifai, Mahmoud; Mathews, Lena M.; Michos, Erin D.

2016-01-01

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality among women. Despite improvements in cardiovascular disease prevention efforts, there remain gaps in cardiovascular disease awareness among women, as well as age and racial disparities in ASCVD outcomes for women. Disparity also exists in the impact the traditional risk factors confer on ASCVD risk between women and men, with smoking and diabetes both resulting in stronger relative risks in women compared to men. Additionally there are risk factors that are unique to women (such as pregnancy-related factors) or that disproportionally affect women (such as auto-immune disease) where preventive efforts should be targeted. Risk assessment and management must also be sex-specific to effectively reduce cardiovascular disease and improve outcomes among women. Evidence supports the use of statin therapy for primary prevention in women at higher ASCVD risk. However, some pause should be given to prescribing aspirin therapy in women without known ASCVD, with most evidence supporting the use of aspirin for women≥65 years not at increased risk for bleeding. This review article will summarize (1) traditional and non-traditional assessments of ASCVD risk and (2) lifestyle and pharmacologic therapies for the primary prevention of ASCVD in women. PMID:28149430

Brachial-Ankle PWV: Current Status and Future Directions as a Useful Marker in the Management of Cardiovascular Disease and/or Cardiovascular Risk Factors.

PubMed

Tomiyama, Hirofumi; Matsumoto, Chisa; Shiina, Kazuki; Yamashina, Akira

2016-01-01

Since 2001, brachial-ankle pulse wave velocity (brachial-ankle PWV) measurement has been applied for risk stratification of patients with atherosclerotic cardiovascular disease and/or its risk factors in Japan. Measurement of the brachial-ankle PWV is simple and well standardized, and its reproducibility and accuracy are acceptable. Several cross-sectional studies have demonstrated a significant correlation between the brachial-ankle PWV and known risk factors for cardiovascular disease; the correlation is stronger in subjects with cardiovascular disease than in those without cardiovascular disease. We conducted a meta-analysis, which demonstrated that the brachial-ankle PWV is an independent predictor of future cardiovascular events. Furthermore, the treatment of cardiovascular risk factors and lifestyle modifications have been shown to improve the brachial-ankle PWV. Thus, at present, brachial-ankle PWV is close to being considered as a useful marker in the management of atherosclerotic cardiovascular disease and/or its risk factors.

Medical therapy is best for atherosclerotic renal artery stenosis: Arguments for.

PubMed

Annigeri, R A

2012-01-01

Atherosclerotic renal artery stenosis (ARAS) is a common condition that causes hypertension and reduction in the glomerular filtration rate and is an independent risk factor for death. Despite high technical success, the clinical benefit of renal artery (RA) angioplasty with stenting in ARAS remains doubtful. The published randomized clinical trials provide no support for the notion that renal angioplasty with stenting significantly improves blood pressure, preserves renal function, or reduces episodes of congestive heart failure in patients with ARAS. RA stenting is associated with procedure-related morbidity and mortality. Agents to block the renin-angiotensin-aldosterone system improve outcome and should be a part of a multifaceted medical regimen in ARAS. Medical therapy effectively controls atherosclerotic renovascular disease at all levels of vasculature and hence is the best therapy for ARAS.

Cardiovascular disease risk factors and cognitive impairment.

PubMed

Nash, David T; Fillit, Howard

2006-04-15

The role of cardiovascular disease risk factors in the occurrence and progression of cognitive impairment has been the subject of a significant number of publications but has not achieved widespread recognition among many physicians and educated laymen. It is apparent that the active treatment of certain of these cardiovascular disease risk factors is accompanied by a reduced risk for cognitive impairment. Patients with hypertension who are treated experience fewer cardiovascular disease events as well as less cognitive impairment than similar untreated patients. Patients who exercise may present with less cognitive impairment, and obesity may increase the risk for cognitive impairment. Lipid abnormalities and genetic markers are associated with an increased risk for cardiovascular disease and cognitive impairment. Autopsy studies have demonstrated a correlation between elevated levels of cholesterol and amyloid deposition in the brain. Research has demonstrated a relation between atherosclerotic obstruction lesions in the circle of Willis and dementia. Diabetes mellitus is associated with an increased risk for cardiovascular disease and cognitive impairment. A number of nonpharmacologic factors have a role in reducing the risk for cognitive impairment. Antioxidants, fatty acids, and micronutrients may have a role, and diets rich in fruits and vegetables and other dietary approaches may improve the outlook for patients considered at risk for cognitive impairment.

Polymorphisms in NOS3, MTHFR, APOB and TNF-α Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients

PubMed Central

Heidari, Mohammad Mehdi; Khatami, Mehri; Hadadzadeh, Mehdi; Kazemi, Mahbobeh; Mahamed, Sahar; Malekzadeh, Pegah; Mirjalili, Massomeh

2015-01-01

Background: Atherosclerosis is a complex multifocal arterial disease involving interactions between multiple genetic and environmental factors. Objectives: In the present study, we investigated the possible association between NOS3 (rs1799983), MTHFR (rs1801133), APOB (rs5742904) and TNF-α (rs361525) polymorphisms and the risk of coronary atherosclerotic lesions in Iranian patients. Patients and Methods: In the case-control study, 108 patients with coronary atherosclerosis disease and 95 control subjects with no family history of cardiovascular disease were enrolled. Genotypes for NOS3, MTHFR, APOB and TNF-α polymorphisms were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Results: We specifically detected the NOS3 TT genotype in 12 patients (11.11%) and did not find the same genotype in any of the controls. The frequencies of T allele in patients and the controls were 24% and 17.8%, respectively. The prevalence of the MTHFR TT genotype was 16.7% in patients and 2.2% in control groups. The prevalence of the APOB-100 (R3500Q) mutation in this patient population was 0%. The frequency of the A allele in the TNF-α gene was 11.1% and 11% in patients and controls, respectively, and the AA genotype was undetected. Conclusions: Our results show a significant association of NOS3 and MTHFR gene polymorphisms with coronary atherosclerotic lesions. Therefore, these variants might influence the risk of coronary artery disease, specifically in the Iranian population. PMID:26878010

Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions.

PubMed

Häkkinen, T; Luoma, J S; Hiltunen, M O; Macphee, C H; Milliner, K J; Patel, L; Rice, S Q; Tew, D G; Karkola, K; Ylä-Herttuala, S

1999-12-01

We studied the expression of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an enzyme capable of hydrolyzing platelet-activating factor (PAF), PAF-like phospholipids, and polar-modified phosphatidylcholines, in human and rabbit atherosclerotic lesions. Oxidative modification of low-density lipoprotein, which plays an important role in atherogenesis, generates biologically active PAF-like modified phospholipid derivatives with polar fatty acid chains. PAF is known to have a potent proinflammatory activity and is inactivated by its hydrolysis. On the other hand, lysophosphatidylcholine and oxidized fatty acids released from oxidized low-density lipoprotein as a result of Lp-PLA(2) activity are thought to be involved in the progression of atherosclerosis. Using combined in situ hybridization and immunocytochemistry, we detected Lp-PLA(2) mRNA and protein in macrophages in both human and rabbit atherosclerotic lesions. Reverse transcriptase-polymerase chain reaction analysis indicated an increased expression of Lp-PLA(2) mRNA in human atherosclerotic lesions. In addition, approximately 6-fold higher Lp-PLA(2) activity was detected in atherosclerotic aortas of Watanabe heritable hyperlipidemic rabbits compared with normal aortas from control rabbits. It is concluded that (1) macrophages in both human and rabbit atherosclerotic lesions express Lp-PLA(2), which could cleave any oxidatively modified phosphatidylcholine present in the lesion area, and (2) modulation of Lp-PLA(2) activity could lead to antiatherogenic effects in the vessel wall.

Association between abdominal fat distribution and atherosclerotic changes in the carotid artery.

PubMed

Oike, Miki; Yokokawa, Hirohide; Fukuda, Hiroshi; Haniu, Tomomi; Oka, Fukuko; Hisaoka, Teruhiko; Isonuma, Hiroshi

2014-01-01

We aimed to evaluate the association between abdominal fat distribution (e.g., abdominal visceral fat area [VFA], subcutaneous fat area [SFA], and total fat area [TFA]), waist circumference (WC), or body mass index (BMI) and atherosclerotic changes in the carotid artery after adjusting for common risk factors. The present study is a hospital-based, cross-sectional study. Study participants included 223 Japanese individuals who underwent a medical health checkup at Juntendo University Hospital, Tokyo, between December 2005 and August 2011. Multivariate logistic regression analysis was used to examine the association between abdominal VFA, SFA, TFA, the VFA/SFA ratio, WC, or BMI and intima-media thickness [IMT] (mean IMT≥1.1mm or maximum IMT≥1.2mm) as atherosclerotic changes in the carotid artery. Multivariate logistic regression analysis showed that VFA (OR for ≥150cm(2) versus <100cm(2), 3.88; 95% CI, 1.39-10.85), BMI (OR for ≥27.6kg/m(2) versus <25kg/m(2), 5.22; 95% CI, 1.69-16.16), and TFA (OR for 200-285cm(2) versus <200cm(2), 4.15; 95% CI, 1.34-12.86: OR for ≥285cm(2) versus <200cm(2), 5.53; 95% CI, 1.76-17.35) were significantly associated with atherosclerotic changes in men. After adjustment for BMI, only TFA (OR for ≥285cm(2) versus <200cm(2), 3.76; 95%CI, 1.03-13.79) in men was significantly associated with atherosclerotic changes in the carotid artery. Our results indicate that VFA, TFA, and BMI are independently associated with atherosclerotic changes in Japanese men. TFA may be considered as a valuable measure of atherosclerotic changes. Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

A Salmon Protein Hydrolysate Exerts Lipid-Independent Anti-Atherosclerotic Activity in ApoE-Deficient Mice

PubMed Central

Busnelli, Marco; Bjørndal, Bodil; Holm, Sverre; Brattelid, Trond; Manzini, Stefano; Ganzetti, Giulia S.; Dellera, Federica; Halvorsen, Bente; Aukrust, Pål; Sirtori, Cesare R.; Nordrehaug, Jan E.; Skorve, Jon; Berge, Rolf K.; Chiesa, Giulia

2014-01-01

Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD)-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo) E−/− mice were divided into two groups and fed a high-fat diet with or without 5% (w/w) SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in the 12 apoE−/− mice fed 5% SPH for 12 weeks compared to the 12 casein-fed control mice. Immunohistochemical characterization of atherosclerotic lesions in aortic sinus displayed no differences in plaque composition between mice fed SPH compared to controls. However, reduced mRNA level of Icam1 in the aortic arch was found. The plasma content of arachidonic acid (C20∶4n-6) and oleic acid (C18∶1n-9) were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1β, IL-6, TNF-α and GM-CSF, whereas plasma cholesterol and triacylglycerols (TAG) were unchanged, accompanied by unchanged mitochondrial fatty acid oxidation and acyl-CoA:cholesterol acyltransferase (ACAT)-activity. These data show that a 5% (w/w) SPH diet reduces atherosclerosis in apoE−/− mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids or fatty acids. PMID:24840793

Rationale, Design, and Methodological Aspects of the BUDAPEST-GLOBAL Study (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions).

PubMed

Maurovich-Horvat, Pál; Tárnoki, Dávid L; Tárnoki, Ádám D; Horváth, Tamás; Jermendy, Ádám L; Kolossváry, Márton; Szilveszter, Bálint; Voros, Viktor; Kovács, Attila; Molnár, Andrea Á; Littvay, Levente; Lamb, Hildo J; Voros, Szilard; Jermendy, György; Merkely, Béla

2015-12-01

The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST-GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single-center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same-sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non-contrast-enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non-contrast-enhanced image slice was acquired at the level of L3-L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3-dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per-patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST-GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders. © 2015 Wiley Periodicals, Inc.

Association of Monocyte Chemoattractant Protein-1 with Death and Atherosclerotic Events in Chronic Kidney Disease.

PubMed

Gregg, L Parker; Tio, Maria Clarissa; Li, Xilong; Adams-Huet, Beverley; de Lemos, James A; Hedayati, S Susan

2018-06-06

Monocyte chemoattractant protein-1 -(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored. In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8%) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events. MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = -0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7%) deaths and 168 (6.4%) atherosclerotic events in the non-CKD vs. 97 (34.0%) deaths and 62 (27.9%) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4-2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0-2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1-2.3]) after adjusting for CV risk factors. Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD. © 2018 S. Karger AG, Basel.

Emerging Technology Update Intravascular Photoacoustic Imaging of Vulnerable Atherosclerotic Plaque.

PubMed

Wu, Min; Fw van der Steen, Antonius; Regar, Evelyn; van Soest, Gijs

2016-10-01

The identification of vulnerable atherosclerotic plaques in the coronary arteries is emerging as an important tool for guiding atherosclerosis diagnosis and interventions. Assessment of plaque vulnerability requires knowledge of both the structure and composition of the plaque. Intravascular photoacoustic (IVPA) imaging is able to show the morphology and composition of atherosclerotic plaque. With imminent improvements in IVPA imaging, it is becoming possible to assess human coronary artery disease in vivo . Although some challenges remain, IVPA imaging is on its way to being a powerful tool for visualising coronary atherosclerotic features that have been specifically associated with plaque vulnerability and clinical syndromes, and thus such imaging might become valuable for clinical risk assessment in the catheterisation laboratory.

Atherosclerotic vascular disease in systemic lupus erythematosus.

PubMed

Liang, Matthew H; Mandl, Lisa A; Costenbader, Karen; Fox, Ervin; Karlson, Elizabeth

2002-09-01

In the United States, systemic lupus erythematosus (SLE) disproportionately affects African Americans. It has become a chronic disease with long-term morbidity including chronic renal disease, osteoporosis, cataracts, psychosocial impairment, and importantly, atherosclerotic vascular disease (ASVD). The latter (myocardial infarction, angina, peripheral vascular disease and stroke) are strikingly accelerated, occurring in subjects who are predominantly premenopausal women at an age when ASVD is rare or unusual. Although much is known about the biology, risk factors, and the prevention of atherosclerosis in normal individuals, little work has been done in SLE. In fact, ASVD in people with SLE may be a different disease. Approximately 1.5% of SLE patients per year will have a myocardial infarction or equivalent; about 0.5% of SLE patients per year will have a stroke. The risk factors for ASVD in SLE are based on small, retrospective, single center studies. These suggest that the risk factors known for the general population (i.e., smoking, obesity, sedentary lifestyle, high LDL cholesterol, etc.) are also observed in SLE. The best study of risk factors shows that even accounting for the known factors, SLE and/or its treatment (glucocorticoids) is by far the most important. Our current management of cardiovascular risk factors in SLE patients with ASVD is substandard and our adherence to national guidelines for prevention is substandard. It is not known whether improving either will prevent these disastrous outcomes. Very little is known about the risk factors in African Americans with SLE, although there is data to suggest that they may not be identical to those seen in Caucasian populations. The study of the best and most effective means to prevent ASVD in SLE and in African Americans with SLE and in African Americans with SLE should be a major priority.

Application of infrared fiber optic imaging in atherosclerotic plaques

NASA Astrophysics Data System (ADS)

Guo, Bujin; Casscells, S. W.; Bearman, Gregory H.; McNatt, Janice; Naghevi, Morteza; Malik, Basit A.; Gul, Khawar; Willerson, James T.

1999-07-01

Rupture of atherosclerotic plaques - the main cause of heart attach and stokes - is not predictable. Hence even treadmill stress tests fail to detect many persons at risk. Fatal plaques are found at autopsies to be associated with active inflammatory cells. Classically, inflammation is detected by its swelling, red color, pain and heat. We have found that heat accurately locates the dangerous plaques that are significantly warmer then atherosclerotic plaques without the same inflammation. In order to develop a non-surgical method of locating these plaques, an IR fiber optic imaging system has been developed in our laboratory to evalute the causes and effect of heat in atherosclerotic plaques. The fiber optical imagin bundle consists of 900 individual As2S3 chalcogenide glass fibers which transmit IR radiation from 0.7 micrometers 7 micrometers with little energy loss. By combining that with a highly sensitive Indium Antimonide IR focal plane array detector, we are able to obtain thermal graphic images in situ. The temperature heterogeneity of atherosclerotic plaques developed in the arteral of the experimental animal models is under study with the new device. The preliminary experimental results from the animal model are encouraging. The potential of using this new technology in diagnostic evaluation of the vulnerable atherosclerotic plaques is considerable.

Impact and risk factors of post-stroke bone fracture

PubMed Central

Huo, Kang; Hashim, Syed I; Yong, Kimberley L Y; Su, Hua; Qu, Qiu-Min

2016-01-01

Bone fracture occurs in stroke patients at different times during the recovery phase, prolonging recovery time and increasing medical costs. In this review, we discuss the potential risk factors for post-stroke bone fracture and preventive methods. Most post-stroke bone fractures occur in the lower extremities, indicating fragile bones are a risk factor. Motor changes, including posture, mobility, and balance post-stroke contribute to bone loss and thus increase risk of bone fracture. Bone mineral density is a useful indicator for bone resorption, useful to identify patients at risk of post-stroke bone fracture. Calcium supplementation was previously regarded as a useful treatment during physical rehabilitation. However, recent data suggests calcium supplementation has a negative impact on atherosclerotic conditions. Vitamin D intake may prevent osteoporosis and fractures in patients with stroke. Although drugs such as teriparatide show some benefits in preventing osteoporosis, additional clinical trials are needed to determine the most effective conditions for post-stroke applications. PMID:26929915

Peripheral ARtery Atherosclerotic DIsease and SlEep disordered breathing (PARADISE) trial - protocol for an observational cohort study.

PubMed

Szymański, Filip M; Gałązka, Zbigniew; Płatek, Anna E; Górko, Dariusz; Ostrowski, Tomasz; Adamkiewicz, Karolina; Łęgosz, Paweł; Ryś, Anna; Semczuk-Kaczmarek, Karolina; Celejewski, Krzysztof; Filipiak, Krzysztof J

2017-01-01

Peripheral arterial disease (PAD) is in fact a group of disease entities with different symptoms and course but a common underlying cause, i.e. atherosclerosis. Atherosclerosis is known to be aggravated by several cardiovascular risk factors, including obstructive sleep apnoea (OSA). Following paper is a protocol for the Peripheral ARtery Atherosclerotic DIsease and SlEep disordered breathing (PARADISE) trial, which aims to describe the prevalence of OSA in PAD patients scheduled for revascularisation, and to determine the effect of OSA on the procedure outcomes. The PARADISE study is an observational cohort trial. It plans to include 200 consecutive patients hospitalised for revascularisation due to PAD. In every patient an overnight sleep study will be performed to diagnose sleep disorders. Accord¬ing to the results of the test, patients will be divided into two groups: group A - patients with OSA, and group B - patients without OSA (control group). All patients will also be screened for classical and non-classical cardiovascular risk factors. In some of the patients, during surgery, a fragment of atherosclerotic plaque will be collected for further testing. Patients will be followed for one year for adverse events and end-points. Primary end-point of the study will be the failure of revascularisa¬tion defined as recurrence or new onset of the symptoms of ischaemia from the treated region, a need for re-operation or procedure revision, or recurrence of ischaemia signs on the imaging tests. The data obtained will help determine the incidence of OSA in the population of patients with PAD. The au¬thors expect to show that, as with other cardiovascular diseases associated with atherosclerosis, also in patients with PAD the incidence of undiagnosed OSA is high and its presence is associated with elevated cholesterol, inflammatory markers, and higher prevalence of arterial hypertension and poor control of other cardiovascular risk factors. In addition, due to

Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

PubMed Central

Picano, Eugenio; Paterni, Marco

2015-01-01

A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques—such as vascular, transesophageal, and intravascular ultrasound—on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque), iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque), and markedly hyperechoic with shadowing (calcific plaque). Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics) are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging, offering unique

Icaritin Inhibits Collagen Degradation-Related Factors and Facilitates Collagen Accumulation in Atherosclerotic Lesions: A Potential Action for Plaque Stabilization

PubMed Central

Zhang, Zong-Kang; Li, Jie; Yan, De-Xin; Leung, Wing-Nang; Zhang, Bao-Ting

2016-01-01

Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium-derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits were fed with an atherogenic diet for four months. Oral administration of ICT (10 mg·kg−1·day−1) was started after two months of an atherogenic diet and lasted for two months. The collagen degradation-related parameters, including macrophages accumulation, content and activity of interstitial collagenase-1 (MMP-1), and the collagen synthesis-related parameters, including amount and distribution of smooth muscle cells (SMC) and collagen mRNA/protein levels, were evaluated in the aorta. ICT reduced plasma lipid levels, inhibited macrophage accumulation, lowered MMP-1 mRNA and protein expression, and suppressed proteolytic activity of pro-MMP-1 and MMP-1 in the aorta. ICT changed the distribution of the SMCs towards the fibrous cap of lesions without increasing the amount of SMCs. Higher collagen protein content in lesions and aorta homogenates was observed with ICT treatment compared with the atherogenic diet only, without altered collagen mRNA level. These results suggest that ICT could inhibit the collagen degradation-related factors and facilitate collagen accumulation in atherosclerotic lesions, indicating a new potential of ICT in atherosclerotic plaques. PMID:26828485

Different components of blood pressure are associated with increased risk of atherosclerotic cardiovascular disease versus heart failure in advanced chronic kidney disease

PubMed Central

Bansal, Nisha; McCulloch, Charles E.; Lin, Feng; Robinson-Cohen, Cassianne; Rahman, Mahboob; Kusek, John W.; Anderson, Amanda H.; Xie, Dawei; Townsend, Raymond R.; Lora, Claudia M.; Wright, Jackson; Go, Alan S.; Ojo, Akinlolu; Alper, Arnold; Lustigova, Eva; Cuevas, Magda; Kallem, Radhakrishna; Hsu, Chi-yuan

2016-01-01

Blood pressure is a modifiable risk for cardiovascular disease (CVD). Among hemodialysis patients, there is a U-shaped association between blood pressure and risk of death. However, few studies have examined the association between blood pressure and CVD in patients with stage 4 and 5 chronic kidney disease. Here we studied 1,795 Chronic Renal Insufficiency Cohort (CRIC) Study participants with estimated glomerular filtration rate under 30 ml/min/1.73 m2 and not on dialysis. The association of systolic (SBP), diastolic (DBP) and pulse pressure with risk of physician-adjudicated atherosclerotic CVD (stroke, myocardial infarction or peripheral arterial disease) and heart failure were tested using Cox regression adjusted for demographics, comorbidity and medications. There was a significant association with higher SBP (adjusted hazard ratio 2.04 [95% confidence interval: 1.46, 2.84]) for SBP over 140 vs under 120 mmHg, higher DBP (2.52 [1.54, 4.11]) for DBP over 90 vs under 80 mmHg and higher pulse pressure (2.67 [1.82, 3.92]) for pulse pressure over 68 vs under 51 mmHg with atherosclerotic CVD. For heart failure, there was a significant association with higher pulse pressure only (1.42 [1.05, 1.92]) for pulse pressure over 68 vs under 51 mmHg, but not for SBP or DBP. Thus, among participants with stage 4 and 5 chronic kidney disease, there was an independent association between higher SBP, DBP and pulse pressure with risk of atherosclerotic CVD, while only higher pulse pressure was independently associated with greater risk of heart failure. Further trials are needed to determine whether aggressive reduction of blood pressure reduces the risk of CVD events in patients with stage 4 and 5 chronic kidney disease. PMID:27717485

Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

PubMed Central

2014-01-01

Background The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. Methods A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. Results After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. Conclusions The prevalence and risk of lower limb

Endovascular Management of Atherosclerotic Renal Artery Stenosis: Post-Cardiovascular Outcomes in Renal Atherosclerotic Lesions Era Winner or False Alarm?

PubMed Central

Karanikola, Evridiki; Karaolanis, Georgios; Galyfos, George; Barbaressos, Emmanuel; Palla, Viktoria; Filis, Konstantinos

2017-01-01

Renal artery stenosis (RAS) is frequently associated with severe comorbidities such as reduced renal perfusion, hypertension, and end-stage renal failure. In approximately 90% of patients, renal artery atherosclerosis is the main cause for RAS, and it is associated with an increased risk for fatal and non-fatal cardiovascular and renal complications. Endovascular management of atherosclerotic RAS (ARAS) has been recently evaluated by several randomized controlled trials that failed to demonstrate benefit of stenting. Furthermore, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions study did not demonstrate any benefit over the revascularization approach. In this review, we summarized the available data from retrospective, prospective and randomized trials on ARAS to provide clinicians with sufficient data in order to produce useful conclusions for everyday clinical practice. PMID:28377906

Revascularization to preserve renal function in patients with atherosclerotic renovascular disease.

PubMed

Novick, A C; Textor, S C; Bodie, B; Khauli, R B

1984-08-01

There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

PubMed

Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

[Effects of berberine on serum inflammatory factors and carotid atherosclerotic plaques in patients with acute cerebral ischemic stroke].

PubMed

Li, Ying; Wang, Pei; Chai, Mei-Jing; Yang, Fan; Li, Hong-Shan; Zhao, Jing; Wang, Huan; Lu, Dan-Dan

2016-11-01

This study aims to analyze the effect of berberine on serum inflammatory factors and carotid atherosclerotic plaques in ppatients with acute cerebral ischemic stroke(AIS). In the study, 120 patients with AIS were randomly divided into berberine group(n=60) and general group (n=60). The 60 cases in the general group were provided with general therapy according to the latest guidelines of diagnosis and treatment of AIS. The berberine group received berberine 300 mg(tid) in addition to the therapy of the general group. The levels of serum inflammatory factors, the nerve function defect grades and the indexes of carotid atherosclerosis plaques [including the total plaque area(TPA), intima-media thickness(IMT) and the number of unstable carotid atherosclerotic plaques] were measured and compared. The results indicated that the levels of serum inflammatory factors, the NIHSS(national institute of health stroke scales) cores and the indexes of carotid atherosclerosis plaques were not significantly different between the berberine groups of general group, with positive correlation between serum inflammatory factors and NIHSS scores(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine groups on 14 d were significantly lower than those on 1 d(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine group on 14 d were significantly lower than those of the general group(P<0.05). The TPA and the number of unstable carotid atherosclerotic plaques of the berberine groups on 90 d were significantly lower than those of general group, with significant differences(P<0.05). The IMT showed a downward trend, but with significant difference.The mRS(modified rankin scale) scores of the berberine group on 90 d were significantly lower, with a higher rate of short-term favorable prognosis (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. This study showed that berberine in

Inflammation in renal atherosclerotic disease.

PubMed

Udani, Suneel M; Dieter, Robert S

2008-07-01

The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

Cadmium exposure and atherosclerotic carotid plaques –Results from the Malmö diet and Cancer study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.se; Barregard, Lars, E-mail: lars.barregard@amm.gu.se; Sallsten, Gerd, E-mail: gerd.sallsten@amm.gu.se

Background: Epidemiological studies indicate that cadmium exposure through diet and smoking is associated with increased risk of cardiovascular disease. There are few data on the relationship between cadmium and plaques, the hallmark of underlying atherosclerotic disease. Objectives: To examine the association between exposure to cadmium and the prevalence and size of atherosclerotic plaques in the carotid artery. Methods: A population sample of 4639 Swedish middle-aged women and men was examined in 1991–1994. Carotid plaque was determined by B-mode ultrasound. Cadmium in blood was analyzed by inductively coupled plasma mass spectrometry. Results: Comparing quartile 4 with quartile 1 of blood cadmium,more » the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6–2.2) after adjustment for sex and, age; 1.4 (1.1–1.8) after additional adjustment for smoking status; 1.4 (1.1–1.7) after the addition of education level and life style factors; 1.3 (1.03–1.8) after additional adjustment for risk factors and predictors of cardiovascular disease. No effect modification by sex was found in the cadmium-related prevalence of plaques. Similarly, ORs for the prevalence of small and large plaques were after full adjustment 1.4 (1.0–2.1) and 1.4 (0.9–2.0), respectively. The subgroup of never smokers showed no association between cadmium and atherosclerotic plaques. Conclusions: These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans. The role of smoking remains unclear. It may both cause residual confounding and be a source of pro-atherogenic cadmium exposure. - Highlights: • Blood cadmium level is associated with atherosclerotic plaques in the carotid artery. • The results extend previous knowledge of cadmium exposure and clinical events. • The role of smoking remains unclear.« less

Association between cardiovascular risk profiles and the presence and extent of different types of coronary atherosclerotic plaque as detected by multidetector computed tomography.

PubMed

Bamberg, Fabian; Dannemann, Nina; Shapiro, Michael D; Seneviratne, Sujith K; Ferencik, Maros; Butler, Javed; Koenig, Wolfgang; Nasir, Khurram; Cury, Ricardo C; Tawakol, Ahmed; Achenbach, Stephan; Brady, Thomas J; Hoffmann, Udo

2008-03-01

To assess the association between cardiovascular risk factors and extent of noncalcified- (NCAP), mixed- (MCAP), and calcified coronary atherosclerotic plaque (CAP). In this cross-sectional study, we included consecutive subjects who presented with chest pain but had no history of coronary artery disease (CAD) and did not develop acute coronary syndrome. Contrast-enhanced 64-slice coronary MDCT was performed to determine the presence of NCAP, MCAP, and CAP for each coronary segment. Among 195 patients (91 women, mean age: 54.6+/-12.0) exclusively NCAP was detected in 11 patients (5.6%). The extent of NCAP decreased and the extent of MCAP and CAP increased with age (P=0.06, P=0.02, and P=0.13, respectively). Hyperlipidemia and family history of CAD were associated with the extent of NCAP after adjusting for other risk factors (P=0.02 and P=0.04, respectively) or for the extent of MCAP and CAP (P=0.02 and P=0.05, respectively). Our data suggest that only a small proportion of individuals have exclusively NCAP and indicate that the relation of NCAP and CAP changes with age. Among individual risk factors, hyperlipidemia and family history of CAD may be associated with the extent of NCAP. Larger observational trials are necessary to confirm our findings.

Potential benefits of eicosapentaenoic acid on atherosclerotic plaques.

PubMed

Nelson, J R; Wani, O; May, H T; Budoff, M

2017-04-01

Residual cardiovascular (CV) risk remains in some patients despite optimized statin therapy and may necessitate add-on therapy to reduce this risk. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, lowers plasma triglyceride levels without raising low-density lipoprotein cholesterol levels and has potential beneficial effects on atherosclerotic plaques. Animal studies have shown that EPA reduces levels of pro-inflammatory cytokines and chemokines. In clinical trials utilizing a wide spectrum of plaque imaging modalities, EPA has shown beneficial effects on plaque characteristics. Studies of patients with coronary artery disease receiving statin therapy suggest that EPA may decrease plaque vulnerability and prevent plaque progression. EPA also decreased pentraxin-3 and macrophage accumulation. A large, randomized, Japanese study reported that EPA plus a statin resulted in a 19% relative reduction in major coronary events at 5years versus a statin alone in patients with hypercholesterolemia (P=0.011). Icosapent ethyl, a high-purity prescription form of EPA ethyl ester, has been shown to reduce triglyceride levels and markers of atherosclerotic inflammation. Results of an ongoing CV outcomes study will further define the potential clinical benefits of icosapent ethyl in reducing CV risk in high-risk patients receiving statin therapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Genesis and growth of extracellular vesicle-derived microcalcification in atherosclerotic plaques

PubMed Central

Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

2015-01-01

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked. PMID:26752654

Elevated serum fibroblast growth factor 23 levels as an indicator of lower extremity atherosclerotic disease in Chinese patients with type 2 diabetes mellitus.

PubMed

He, Xingxing; Hu, Xiang; Ma, Xiaojing; Su, Hang; Ying, Lingwen; Peng, Jiahui; Pan, Xiaoping; Bao, Yuqian; Zhou, Jian; Jia, Weiping

2017-06-15

Recently, basic and clinical studies have provided evidence supporting the relationship between circulating levels of fibroblast growth factor (FGF) 23 and the development of atherosclerosis. Given that diabetes is an established risk factor for lower extremity atherosclerotic disease (LEAD), the goal of the present study was to explore the relationship between serum FGF23 levels and LEAD, as well as the related factors, in Chinese patients with type 2 diabetes mellitus (T2DM). A total of 401 hospitalized T2DM patients (201 subjects with LEAD and 200 subjects without LEAD) were enrolled in this study. Serum FGF23 levels were determined by a sandwich enzyme-linked immunosorbent assay. Femoral intima-media thickness (F-IMT) and lower limb atherosclerotic plaque were assessed through color Doppler ultrasound. The median (interquartile range) serum FGF23 levels in the entire study population was 42.08 (35.59-49.17) pg/mL. Subjects with LEAD had significantly higher serum FGF23 levels compared with those without LEAD (44.00 [37.54-51.30] pg/mL versus 40.42 [32.61-48.23] pg/mL, P < 0.001). Logistic regression showed that serum FGF23 levels were independently and positively correlated with the presence of LEAD (odds ratio 1.039, 95% confidence interval 1.012-1.067, P = 0.004). In addition, multiple liner regression analysis revealed that serum FGF23 levels were positively associated with F-IMT (standardized β = 0.175, P < 0.001). Furthermore, this relationship remained significant after additional adjustment for gender and factors potentially affecting serum FGF23 levels (serum calcium, serum phosphorus, and glomerular filtration rate), respectively (both P < 0.01). In Chinese patients with T2DM, serum FGF23 levels were independently and positively correlated with the presence of LEAD.

A Conceptual Framework for Addressing Residual Atherosclerotic Cardiovascular Disease Risk in the Era of Precision Medicine.

PubMed

Patel, Kershaw V; Pandey, Ambarish; de Lemos, James A

2018-04-11

Until recently, therapies to mitigate atherosclerotic cardiovascular disease (ASCVD) risk have been limited to lifestyle interventions, blood pressure lowering medications, high intensity statin therapy, antiplatelet agents, and in select patients, coronary artery revascularization. Despite administration of these evidence-based therapies, substantial residual risk for cardiovascular events persists, particularly among individuals with known ASCVD. Moreover, the current guideline-based approach does not adequately account for patient-specific, causal pathways that lead to ASCVD progression and complications. In the past few years, multiple new pharmacological agents, targeting conceptually distinct pathophysiological targets, have been shown in large and well-conducted clinical trials to lower cardiovascular risk among patients with established ASCVD receiving guideline directed medical care. These evidenced-based therapies reduce event rates, and in some cases all-cause and cardiovascular mortality; these benefits confirm important new disease targets and challenge the adequacy of the current "standard of care" for secondary prevention.

Use of Low-dose Aspirin as Secondary Prevention of Atherosclerotic Cardiovascular Disease Among US Adults (From the National Health Interview Survey, 2012)

PubMed Central

Fang, Jing; George, Mary G.; Gindi, Renee M.; Hong, Yuling; Yang, Quanhe; Ayala, Carma; Ward, Brian W.; Loustalot, Fleetwood

2015-01-01

Current guidelines recommend that adults with atherosclerotic cardiovascular disease take low-dose aspirin or other antiplatelet medications as secondary prevention of recurrent cardiovascular events. Yet, no national level assessment of low-dose aspirin use for secondary prevention of cardiovascular disease has been reported among a community-based population. Using data from the 2012 National Health Interview Survey, we assessed low-dose aspirin use among those with atherosclerotic cardiovascular disease. We estimated the prevalence ratios of low-dose aspirin use, adjusting for sociodemographic status, health insurance, and cardiovascular risk factors. Among those with atherosclerotic cardiovascular disease (n=3,068), 76% had been instructed to take aspirin, and 88% of those were following this advice. Of those not advised, 11% took aspirin on this own. Overall, 70% were taking aspirin (including those who followed their health care provider's advice and those who were not advised but took aspirin on their own). Logistic regression models showed that women, non-Hispanic blacks and Hispanics, those aged 40–64 years, with a high school education or with some college, or with fewer cardiovascular disease risk factors were less likely to take aspirin than men, non-Hispanic whites, those aged ≥65 years, with a college education or higher, or with all four selected cardiovascular disease risk factors, respectively. Additional analyses conducted among those with coronary heart disease only (n=2,007) showed similar patterns. In conclusion, use of low-dose aspirin for secondary prevention was 70%, with high reported adherence to health care providers' advice to take low-dose aspirin (88%), and significant variability within subgroups. PMID:25670639

The ACC/AHA 2013 pooled cohort equations compared to a Korean Risk Prediction Model for atherosclerotic cardiovascular disease.

PubMed

Jung, Keum Ji; Jang, Yangsoo; Oh, Dong Joo; Oh, Byung-Hee; Lee, Sang Hoon; Park, Seong-Wook; Seung, Ki-Bae; Kim, Hong-Kyu; Yun, Young Duk; Choi, Sung Hee; Sung, Jidong; Lee, Tae-Yong; Kim, Sung Hi; Koh, Sang Baek; Kim, Moon Chan; Chang Kim, Hyeon; Kimm, Heejin; Nam, Chungmo; Park, Sungha; Jee, Sun Ha

2015-09-01

To evaluate the performance of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 Pooled Cohort Equations in the Korean Heart Study (KHS) population and to develop a Korean Risk Prediction Model (KRPM) for atherosclerotic cardiovascular disease (ASCVD) events. The KHS cohort included 200,010 Korean adults aged 40-79 years who were free from ASCVD at baseline. Discrimination, calibration, and recalibration of the ACC/AHA Equations in predicting 10-year ASCVD risk in the KHS cohort were evaluated. The KRPM was derived using Cox model coefficients, mean risk factor values, and mean incidences from the KHS cohort. In the discriminatory analysis, the ACC/AHA Equations' White and African-American (AA) models moderately distinguished cases from non-cases, and were similar to the KRPM: For men, the area under the receiver operating characteristic curve (AUROCs) were 0.727 (White model), 0.725 (AA model), and 0.741 (KRPM); for women, the corresponding AUROCs were 0.738, 0.739, and 0.745. Absolute 10-year ASCVD risk for men in the KHS cohort was overestimated by 56.5% (White model) and 74.1% (AA model), while the risk for women was underestimated by 27.9% (White model) and overestimated by 29.1% (AA model). Recalibration of the ACC/AHA Equations did not affect discriminatory ability but improved calibration substantially, especially in men in the White model. Of the three ASCVD risk prediction models, the KRPM showed best calibration. The ACC/AHA Equations should not be directly applied for ASCVD risk prediction in a Korean population. The KRPM showed best predictive ability for ASCVD risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Risk factor management: antiatherogenic therapies.

PubMed

Gielen, Stephan; Sandri, Marcus; Schuler, Gerhard; Teupser, Daniel

2009-08-01

Despite the advances in interventional techniques, the management of stable atherosclerosis remains the domain of optimal guideline-oriented therapy. Recent studies on the effects of aggressive lipid lowering on atheroma volume changes using intravascular ultrasound indicate that it is possible to achieve atherosclerosis regression by reaching low-density lipoprotein (LDL) levels less than 75 mg/dl. The pleiotropic anti-inflammatory effects of statins contribute to the reduction of cardiovascular (CV) event observed with aggressive lipid lowering. As a second important strategy to prevent disease progression, lifestyle changes with regular physical exercise are capable of halting the atherosclerotic process and reducing angina symptoms and CV events. Optimal medical therapy, a healthy lifestyle with regular physical exercise, and coronary interventions are not mutually exclusive treatment strategies. Over the last few decades, both have proved to be effective in significantly reducing the CV mortality in the Western world. However, risk factor modification contributed to at least half the effect in the reduction of CV mortality. This figure provides an estimate of what could be achieved if we were to take risk factor modification more seriously - especially in the acute care setting. The knowledge is there: today we have a better understanding on how to stop progression and even induce regression of atherosclerosis. Much research still needs to be done and will be done. In the meantime, however, our primary focus should lie in implementing what is already known. In addition, it is essential not just to treat CV risk factors, but also to treat them to achieve the target values as set by the guidelines of European Society of Cardiology.

How does juxtaluminal calcium affect critical mechanical conditions in carotid atherosclerotic plaque? An exploratory study.

PubMed

Zhongzhao Teng; Jing He; Sadat, Umar; Mercer, John R; Xiaoyan Wang; Bahaei, Nasim S; Thomas, Owen M; Gillard, Jonathan H

2014-01-01

The impact of calcification on the carotid atherosclerotic plaque vulnerability remains controversial and unclear. This study assesses the critical mechanical conditions induced by the calcium at the lumen surface, i.e., juxtaluminal calcification (JLCa), within human carotid atherosclerotic plaque. Eleven patients with evidence of JLCa were included for the analysis. The plaque geometry was reconstructed based on computed tomography and magnetic resonance images and 3-D fluid-structure interaction simulation was used for mechanical analysis. The presence of JLCa increased local stresses compared to when calcification was artificially covered with a 0.2-mm-thick fibrous cap (107.87 kPa [76.99, 129.14] versus 63.17 kPa [34.55, 75.13]; Median, [interquartile range]; ). Stretch ratio decreased from 1.18 [1.07, 1.27] to 1.13 [1.10, 1.18] (p = 0.03). The presence of JLCa significantly elevates local stress and stretch level. Further exploration of this plaque feature is warranted as a possible risk factor causing plaque vulnerability.

Imaging of the Fibrous Cap in Atherosclerotic Carotid Plaque

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saba, Luca, E-mail: lucasaba@tiscali.i; Potters, Fons; Lugt, Aad van der

2010-08-15

In the last two decades, a substantial number of articles have been published to provide diagnostic solutions for patients with carotid atherosclerotic disease. These articles have resulted in a shift of opinion regarding the identification of stroke risk in patients with carotid atherosclerotic disease. In the recent past, the degree of carotid artery stenosis was the sole determinant for performing carotid intervention (carotid endarterectomy or carotid stenting) in these patients. We now know that the degree of stenosis is only one marker for future cerebrovascular events. If one wants to determine the risk of these events more accurately, other parametersmore » must be taken into account; among these parameters are plaque composition, presence and state of the fibrous cap (FC), intraplaque haemorrhage, plaque ulceration, and plaque location. In particular, the FC is an important structure for the stability of the plaque, and its rupture is highly associated with a recent history of transient ischaemic attack or stroke. The subject of this review is imaging of the FC.« less

Contemporary medical therapies of atherosclerotic carotid artery disease.

PubMed

Cheng, Suk F; Brown, Martin M

2017-03-01

Contemporary medical therapy consists of identification and treatment of all patient-modifiable vascular risk factors. Specific atherosclerotic disease therapies are designed to reduce the risk of thrombosis, and the disease progression in order to reduce the risk of future cardiovascular events. Contemporary medical management emphasizes the need to support the patient in achieving lifestyle modifications and to adjust medication to achieve individualized target values for specific quantifiable risk factors. Antiplatelet therapy in the form of aspirin or clopidogrel is routinely used for the prevention of ischemic stroke in patients who have had a transient ischemic attack or stroke. There is evidence from a recent trial that the use of combination antiplatelet therapy with aspirin and clopidogrel started within 24 hours of minor stroke or transient ischemic attack reduces the risk of recurrent stroke compared to the use of aspirin alone, and therefore we use aspirin plus clopidogrel in recently symptomatic patients with carotid stenosis pending carotid revascularization. Anticoagulation with heparins or vitamin K antagonist is not recommended except in patients at risk for cardio-embolic events. Lowering blood pressure to target levels has been shown to slow down the progression of carotid artery stenosis and reduces the intima-media thickness of the carotid plaque, while lowering lipid levels with statins has become an essential element in the medical therapy of carotid artery stenosis. Diabetes management should be optimized. Lifestyle choices, including tobacco smoking, physical inactivity, unhealthy diet, obesity, and excessive alcohol intake, are all important modifiable vascular risk factors. The combination of dietary modification, physical exercise, and use of aspirin, a statin, and an antihypertensive agent can be expected to give a cumulative relative stroke risk reduction of 80%. The evidence suggests that intensive medical therapy is so effective that

Association Between Modifiable Risk Factors and Pharmaceutical Expenditures Among Adults With Atherosclerotic Cardiovascular Disease in the United States: 2012-2013 Medical Expenditures Panel Survey.

PubMed

Salami, Joseph A; Valero-Elizondo, Javier; Ogunmoroti, Oluseye; Spatz, Erica S; Rana, Jamal S; Virani, Salim S; Blankstein, Ron; Younus, Adnan; Arrieta, Alejandro; Blaha, Michael J; Veledar, Emir; Nasir, Khurram

2017-06-09

Atherosclerotic cardiovascular disease (ASCVD) causes most deaths in the United States and accounts for the highest healthcare spending. The association between the modifiable risk factors (MRFs) of ASCVD and pharmaceutical expenditures are largely unknown. We examined the association between MRFs and pharmaceutical expenditures among adults with ASCVD using the 2012 and 2013 Medical Expenditure Panel Survey. A 2-part model was used while accounting for the survey's complex design to obtain nationally representative results. All costs were adjusted to 2013 US dollars using the gross domestic product deflator. The annual total pharmaceutical expenditure among those with ASCVD was $71.6 billion, 33% of which was for medications for cardiovascular disease and 14% medications for diabetes mellitus. The adjusted relationship between MRFs and pharmaceutical expenditures showed significant marginal increase in average annual pharmaceutical expenditure associated with inadequate physical activity ($519 [95% confidence interval (CI), $12-918; P =0.011]), dyslipidemia ($631 [95% CI, $168-1094; P =0.008]), hypertension: ($1078 [95% CI, $697-1460; P <0.001)], and diabetes mellitus ($2006 [95% CI, $1470-2542]). Compared with those with optimal MRFs (0-1), those with average MRFs (2-3) spent an average of $1184 (95% CI, $805-1564; P <0.001) more on medications, and those with poor MRFs (≥4) spent $2823 (95% CI, $2338-3307; P <0.001) more. Worsening MRFs were proportionally associated with higher annual pharmaceutical expenditures among patients with established ASCVD regardless of non-ASCVD comorbidity. In-depth studies of the roles played by other factors in this association can help reduce medication-related expenditures among ASCVD patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Impact of Replacing the Pooled Cohort Equation With Other Cardiovascular Disease Risk Scores on Atherosclerotic Cardiovascular Disease Risk Assessment (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

PubMed

Qureshi, Waqas T; Michos, Erin D; Flueckiger, Peter; Blaha, Michael; Sandfort, Veit; Herrington, David M; Burke, Gregory; Yeboah, Joseph

2016-09-01

The increase in statin eligibility by the new cholesterol guidelines is mostly driven by the Pooled Cohort Equation (PCE) criterion (≥7.5% 10-year PCE). The impact of replacing the PCE with either the modified Framingham Risk Score (FRS) or the Systematic Coronary Risk Evaluation (SCORE) on assessment of atherosclerotic cardiovascular disease (ASCVD) risk assessment and statin eligibility remains unknown. We assessed the comparative benefits of using the PCE, FRS, and SCORE for ASCVD risk assessment in the Multi-Ethnic Study of Atherosclerosis. Of 6,815 participants, 654 (mean age 61.4 ± 10.3; 47.1% men; 37.1% whites; 27.2% blacks; 22.3% Hispanics; 12.0% Chinese-Americans) were included in analysis. Area under the curve (AUC) and decision curve analysis were used to compare the 3 risk scores. Decision curve analysis is the plot of net benefit versus probability thresholds; net benefit = true positive rate - (false positive rate × weighting factor). Weighting factor = Threshold probability/1 - threshold probability. After a median of 8.6 years, 342 (6.0%) ASCVD events (myocardial infarction, coronary heart disease death, fatal or nonfatal stroke) occurred. All 4 risk scores had acceptable discriminative ability for incident ASCVD events; (AUC [95% CI] PCE: 0.737 [0.713 to 0.762]; FRS: 0.717 [0.691 to 0.743], SCORE (high risk) 0.722 [0.696 to 0.747], and SCORE (low risk): 0.721 [0.696 to 0.746]. At the ASCVD risk threshold recommended for statin eligibility for primary prevention (≥7.5%), the PCE provides the best net benefit. Replacing the PCE with the SCORE (high), SCORE (low) and FRS results in a 2.9%, 8.9%, and 17.1% further increase in statin eligibility. The PCE has the best discrimination and net benefit for primary ASCVD risk assessment in a US-based multiethnic cohort compared with the SCORE or the FRS. Copyright © 2016 Elsevier Inc. All rights reserved.

2016 Consensus statement on prevention of atherosclerotic cardiovascular disease in the Hong Kong population.

PubMed

Cheung, B My; Cheng, C H; Lau, C P; Wong, C Ky; Ma, R Cw; Chu, D Ws; Ho, D Hk; Lee, K Lf; Tse, H F; Wong, A Sp; Yan, B Py; Yan, V Wt

2017-04-01

In Hong Kong, the prevalence of atherosclerotic cardiovascular disease has increased markedly over the past few decades, and further increases are expected. In 2008, the Hong Kong Cardiovascular Task Force released a consensus statement on preventing cardiovascular disease in the Hong Kong population. The present article provides an update on these recommendations. A multidisciplinary group of clinicians comprising the Hong Kong Cardiovascular Task Force-10 cardiologists, an endocrinologist, and a family physician-met in September 2014 and June 2015 in Hong Kong. Guidelines from the American College of Cardiology/American Heart Association, the European Society of Hypertension/European Society of Cardiology, and the Eighth Joint National Committee for the Management of High Blood Pressure were reviewed. Group members reviewed the 2008 Consensus Statement and relevant international guidelines. At the meetings, each topical recommendation of the 2008 Statement was assessed against the pooled recommendations on that topic from the international guidelines. A final recommendation on each topic was generated by consensus after discussion. It is recommended that a formal risk scoring system should be used for risk assessment of all adults aged 40 years or older who have at least one cardiovascular risk factor. Individuals can be classified as having a low, moderate, or high risk of developing atherosclerotic cardiovascular disease, and appropriate interventions selected accordingly. Recommended lifestyle modifications include adopting a healthy eating pattern; maintaining a low body mass index; quitting smoking; and undertaking regular, moderate-intensity physical activity. Pharmacological interventions should be selected as appropriate after lifestyle modification.

Increased risks of mortality and atherosclerotic complications in incident hemodialysis patients subsequently with bone fractures: a nationwide case-matched cohort study.

PubMed

Kuo, Chiu-Huang; Hsieh, Tsung-Cheng; Wang, Chih-Hsien; Chou, Chu-Lin; Lai, Yu-Hsien; Chen, Yi-Ya; Lin, Yu-Li; Wu, Sheng-Teng; Fang, Te-Chao

2015-01-01

Hemodialysis (HD) patients with bone fractures have an increased risk for death. However, the risks for mortality and atherosclerotic complications in incident HD patients subsequently with bone fractures are unknown. Data derived from the Taiwan National Health Institute Research Database between January 1997 and December 2008 was analyzed. The enrolled patients included 3,008 incident HD patients subsequently with a single long bone fracture (LB Fx) and 2,070 incident HD patients subsequently with a single non-long bone fracture (NLB Fx). These patients were matched (1:5 ratio) for age, sex, and same duration of HD with incident HD patients who had no fractures and outcomes were measured over a 3-year follow-up. After demographic and co-morbidity adjustment, LB Fx increased the risk for overall mortality (HR = 1.59, p < 0.001) and stroke (HR = 1.09, p = 0.028) in incident HD patients. NLB Fx increased the risk for overall mortality (HR = 1.52, p < 0.001), stroke (HR = 1.19, p < 0.001), coronary artery disease (CAD), (HR = 1.13, p = 0.003), and peripheral arterial occlusive disease (PAOD), (HR = 1.41, p < 0.001) in incident HD patients. Moreover, incident patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx. The rates of mortality and stroke were significantly higher in incident HD patients subsequently with bone fractures than in matched patients without bone fractures. Incident HD patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx and without bone fractures. Thus, incident HD patients subsequently with bone fractures should be closely followed for a higher mortality and possible development of atherosclerotic complications.

Increased Risks of Mortality and Atherosclerotic Complications in Incident Hemodialysis Patients Subsequently with Bone Fractures: A Nationwide Case-Matched Cohort Study

PubMed Central

Kuo, Chiu-Huang; Hsieh, Tsung-Cheng; Wang, Chih-Hsien; Chou, Chu-Lin; Lai, Yu-Hsien; Chen, Yi-Ya; Lin, Yu-Li; Wu, Sheng-Teng; Fang, Te-Chao

2015-01-01

Background Hemodialysis (HD) patients with bone fractures have an increased risk for death. However, the risks for mortality and atherosclerotic complications in incident HD patients subsequently with bone fractures are unknown. Methods Data derived from the Taiwan National Health Institute Research Database between January 1997 and December 2008 was analyzed. The enrolled patients included 3,008 incident HD patients subsequently with a single long bone fracture (LB Fx) and 2,070 incident HD patients subsequently with a single non-long bone fracture (NLB Fx). These patients were matched (1:5 ratio) for age, sex, and same duration of HD with incident HD patients who had no fractures and outcomes were measured over a 3-year follow-up. Results After demographic and co-morbidity adjustment, LB Fx increased the risk for overall mortality (HR = 1.59, p < 0.001) and stroke (HR = 1.09, p = 0.028) in incident HD patients. NLB Fx increased the risk for overall mortality (HR = 1.52, p < 0.001), stroke (HR = 1.19, p < 0.001), coronary artery disease (CAD), (HR = 1.13, p = 0.003), and peripheral arterial occlusive disease (PAOD), (HR = 1.41, p < 0.001) in incident HD patients. Moreover, incident patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx. Conclusions The rates of mortality and stroke were significantly higher in incident HD patients subsequently with bone fractures than in matched patients without bone fractures. Incident HD patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx and without bone fractures. Thus, incident HD patients subsequently with bone fractures should be closely followed for a higher mortality and possible development of atherosclerotic complications. PMID:25874794

Quantitative analysis of the polarization characteristics of atherosclerotic plaques

NASA Astrophysics Data System (ADS)

Gubarkova, Ekaterina V.; Kirillin, Michail Y.; Dudenkova, Varvara V.; Kiseleva, Elena B.; Moiseev, Alexander A.; Gelikonov, Grigory V.; Timofeeva, Lidia B.; Fiks, Ilya I.; Feldchtein, Felix I.; Gladkova, Natalia D.

2016-04-01

In this study we demonstrate the capability of cross-polarization optical coherence tomography (CP OCT) to assess collagen and elastin fibers condition in atherosclerotic plaques basing on ratio of the OCT signal levels in cross- and co- polarizations. We consider the depolarization factor (DF) and the effective birefringence (Δn) as quantitative characteristics of CP OCT images. We revealed that calculation of both DF and Δn in the region of interest (fibrous cap) yields a statistically significant difference between stable and unstable plaques (0.46+/-0.21 vs 0.09+/-0.04 for IDF; (4.7+/-1.0)•10-4 vs (2.5+/-0.7)•10-4 for Δn p<0.05). In parallel with CP OCT we used the nonlinear microscopy for analysis of thin cross-section of atherosclerotic plaque, revealing the different average isotropy index of collagen and elastin fibers for stable and unstable plaques (0.30 +/- 0.10 vs 0.70 +/- 0.08; p<0.001). The proposed approach for quantitative assessment of CP OCT images allows cross-scattering and birefringence characterization of stable and unstable atherosclerotic plaques.

Comparison of common carotid artery intima-media thickness between Brazilian Euro-descendants and Afro-descendants with atherosclerosis risk factors.

PubMed

Casella, Ivan Benaduce; Sotelo, Fabio José Bonafé; Yamazaki, Yumiko; Presti, Calógero; Vassoler, Alecxander; Melo, Henry Augusto Hoffmann

2009-01-01

To compare common carotid intima-media thickness (IMT) between the two major Brazilian ethnic groups (those of African descent and those of European descent) among individuals with one or more risk factors for atherosclerotic disease. Two hundred and six patients with one or more risk factors for atherosclerotic disease were evaluated in a cross-sectional study in which their clinical, ethnic and Demographic characteristics were collected. All patients underwent duplex ultrasound examination of their carotid vessels to obtain IMT measurements. One hundred and fifty-three patients (74.3%) had a carotid IMT greater than 1.0 mm at one or more point of measurement in at least one common carotid artery. There was a significant correlation between older age and mean carotid wall thickness (R=0.479 / P<0.01). Multivariate analysis identified male sex, arterial hypertension and older age as variables associated with increased IMT (P<0.05 for all variables). When IMT was compared between the two ethnic groups in this study, no significant differences were noted. Euro-descendants and Afro-descendants had similar IMT values, even when the groups were stratified by degree of IMT (normal vs. increased) and presence of stroke and/or transient ischemic attack (yes vs. no). The risk factors associated with increased common carotid artery IMT in Brazilian individuals are similar to those in previously described populations. No differences were observed between the two main Brazilian ethnic groups. Longitudinal studies are required for a better evaluation of the incidence, etiologic factors and evolution of carotid intimomedial thickening in this population.

Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

PubMed Central

Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

2016-01-01

Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

Effect of impaired glucose tolerance on atherosclerotic lesion formation: an evaluation in selectively bred mice with different susceptibilities to glucose intolerance.

PubMed

Asai, Akira; Nagao, Mototsugu; Kawahara, Momoyo; Shuto, Yuki; Sugihara, Hitoshi; Oikawa, Shinichi

2013-12-01

Impaired glucose tolerance (IGT) is an independent risk factor for atherosclerotic cardiovascular disease. However, due to the lack of appropriate animal models, the underlying mechanisms for IGT-induced atherosclerosis remain to be elucidated in vivo. We recently used selective breeding to establish 2 mouse lines with distinctively different susceptibilities to diet-induced glucose intolerance, designated selectively bred diet-induced glucose intolerance-resistant (SDG-R) and SDG-prone (SDG-P), respectively. Here, we assessed atherosclerotic lesion formation in these mice. Female SDG-R and SDG-P mice were fed an atherogenic diet (AD; 1.25% cholesterol, 0.5% sodium cholate, and 36% energy as fat) for 20 weeks (8-28 weeks of age). Oral glucose tolerance tests were performed during the AD-feeding period. Atherosclerotic lesion formation was quantitatively analyzed in serial aortic sinus sections by oil red O staining. Plasma lipids were measured after the AD-feeding period. Glucose tolerance was impaired in SDG-P mice as compared to SDG-R mice over the 20-week AD-feeding period. No significant differences were observed in any plasma lipid measurement between the 2 mouse lines. Aortic sinus atherosclerotic lesion formation in SDG-P mice was approximately 4-fold greater than that in SDG-R mice. In 2 mouse lines with different susceptibilities to diet-induced glucose intolerance, IGT accelerated atherosclerotic lesion formation. These mice may therefore serve as useful in vivo models for investigating the causal role of IGT in the pathogenesis of atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mitochondrial DNA damage and vascular function in patients with diabetes mellitus and atherosclerotic cardiovascular disease.

PubMed

Fetterman, Jessica L; Holbrook, Monica; Westbrook, David G; Brown, Jamelle A; Feeley, Kyle P; Bretón-Romero, Rosa; Linder, Erika A; Berk, Brittany D; Weisbrod, Robert M; Widlansky, Michael E; Gokce, Noyan; Ballinger, Scott W; Hamburg, Naomi M

2016-03-31

Prior studies demonstrate mitochondrial dysfunction with increased reactive oxygen species generation in peripheral blood mononuclear cells in diabetes mellitus. Oxidative stress-mediated damage to mitochondrial DNA promotes atherosclerosis in animal models. Thus, we evaluated the relation of mitochondrial DNA damage in peripheral blood mononuclear cells s with vascular function in patients with diabetes mellitus and with atherosclerotic cardiovascular disease. We assessed non-invasive vascular function and mitochondrial DNA damage in 275 patients (age 57 ± 9 years, 60 % women) with atherosclerotic cardiovascular disease alone (N = 55), diabetes mellitus alone (N = 74), combined atherosclerotic cardiovascular disease and diabetes mellitus (N = 48), and controls age >45 without diabetes mellitus or atherosclerotic cardiovascular disease (N = 98). Mitochondrial DNA damage measured by quantitative PCR in peripheral blood mononuclear cells was higher with clinical atherosclerosis alone (0.55 ± 0.65), diabetes mellitus alone (0.65 ± 1.0), and combined clinical atherosclerosis and diabetes mellitus (0.89 ± 1.32) as compared to control subjects (0.23 ± 0.64, P < 0.0001). In multivariable models adjusting for age, sex, and relevant cardiovascular risk factors, clinical atherosclerosis and diabetes mellitus remained associated with higher mitochondrial DNA damage levels (β = 0.14 ± 0.13, P = 0.04 and β = 0.21 ± 0.13, P = 0.002, respectively). Higher mitochondrial DNA damage was associated with higher baseline pulse amplitude, a measure of arterial pulsatility, but not with flow-mediated dilation or hyperemic response, measures of vasodilator function. We found greater mitochondrial DNA damage in patients with diabetes mellitus and clinical atherosclerosis. The association of mitochondrial DNA damage and baseline pulse amplitude may suggest a link between mitochondrial dysfunction and excessive small artery pulsatility with potentially adverse microvascular impact.

Advances in non-invasive drug delivery for atherosclerotic heart disease.

PubMed

Maranhão, Raul C; Tavares, Elaine R

2015-07-01

Apart from statins, anti-platelet agents and invasive procedures, the anti-atherosclerotic medical weaponry for coronary heart disease (CHD) is scarce and only partially protects CHD patients from major adverse cardiac events. Several novel non-invasive strategies are being developed to widen the therapeutic options. Among them, drug delivery tools were tested in vivo encompassing liposomes, micelles, polymeric, metallic and lipid nanoparticles used as carriers of statins, corticosteroids, a bisphosphonate, a glitazone, anti-cancer agents, a mycotoxin, a calcium channel blocker and a compound of traditional Chinese medicine. All preparations improved parameters related to atherosclerotic lesions induced in rabbits, rats and mice and reduced neointima formation in experiments aiming to prevent post-stenting restenosis. In subjects submitted to percutaneous coronary intervention, nanoparticle formulations of paclitaxel and alendronate showed safety but are still not conclusive regarding in-stent late loss. The experience of our group in atherosclerotic rabbits treated with non-protein lipid nanoparticles associated with anti-cancer drugs such as paclitaxel, etoposide and methotrexate is summarized, and preliminary safety data in CHD patients are anticipated. Taken together, these studies show that non-invasive drug-delivery systems may become promising tools to rescue CHD patients from the risks of severe and life-threatening lesions that should be more energetically treated.

Impact of the cardiovascular system-associated adipose tissue on atherosclerotic pathology.

PubMed

Chistiakov, Dimitry A; Grechko, Andrey V; Myasoedova, Veronika A; Melnichenko, Alexandra A; Orekhov, Alexander N

2017-08-01

Cardiac obesity makes an important contribution to the pathogenesis of cardiovascular disease. One of the important pathways of this contribution is the inflammatory process that takes place in the adipose tissue. In this review, we consider the role of the cardiovascular system-associated fat in atherosclerotic cardiovascular pathology and a non-atherosclerotic cause of coronary artery disease, such as atrial fibrillation. Cardiovascular system-associated fat not only serves as the energy store, but also releases adipokines that control local and systemic metabolism, heart/vascular function and vessel tone, and a number of vasodilating and anti-inflammatory substances. Adipokine appears to play an important protective role in cardiovascular system. Under chronic inflammation conditions, the repertoire of signaling molecules secreted by cardiac fat can be altered, leading to a higher amount of pro-inflammatory messengers, vasoconstrictors, profibrotic modulators. This further aggravates cardiovascular inflammation and leads to hypertension, induction of the pathological tissue remodeling and cardiac fibrosis. Contemporary imaging techniques showed that epicardial fat thickness correlates with the visceral fat mass, which is an established risk factor and predictor of cardiovascular disease in obese subjects. However, this correlation is no longer present after adjustment for other covariates. Nevertheless, recent studies showed that pericardial fat volume and epicardial fat thickness can probably serve as a better indicator for atrial fibrillation. Copyright © 2017 Elsevier B.V. All rights reserved.

Dietary intake and coronary risk factors in Peruvian Quechua Indians.

PubMed

Watt, E W; Picon-Reategui, E; Gahagan, H E; Buskirk, E R

1976-06-01

Some of the "risk" factors implicated in the etiology of coronary atherosclerotic heart disease were investigated in sixty Quechua men living in two areas of Peru. Highland Quechua had higher serum triglycerides (mean, 122 vs. 90 mg. per deciliter) than downward migrants. There were no significant differences between the two groups in serum cholesterol (mean 150 vs. 157 mg. per deciliter), body fat (mean, 15 vs. 17%), or blood pressure (mean, 113/72 vs. 114/72 mm Hg). Both groups consumed about 2,500 kcal per man per day, while the highland Quechua consumed more carbohydrate (mean, 66 vs. 51%) and less fat (mean 19 vs. 33%). By American standards, both groups had low serum cholesterol values, as well as low blood pressure.

The relationship between IL-18 and atherosclerotic cardiovascular risk in Egyptian lean women with polycystic ovary syndrome.

PubMed

Dawood, Alaaeldin; Alkafrawy, Nabil; Saleh, Said; Noreldin, Rasha; Zewain, Shimaa

2018-04-01

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. The evidence in support of low-grade inflammation in PCOS as an etiology is emerging. Inflammation is likely to be associated with other prominent aspects of PCOS including insulin resistance (IR) and cardiovascular disease (CVD) risk. Interleukin-18 (IL-18) is considered as a strong marker of inflammation. Evaluation of the relation between serum IL-18 and atherosclerotic CVD (ASCVD) risk in Egyptian lean females with PCO. This study included control group of healthy lean normally menstruating females, lean PCOS group (BMI < 25 kg/m 2 ), and obese PCOS group (BMI > 25 kg/m 2 ) presented with infertility and diagnosed according to Rotterdam criteria. Measurements of serum lipid profile, IR, and IL-18 were done. Lipid accumulation product (LAP), IR and ASCVD risk were significantly higher in PCOS patients (lean and obese) compared to controls and in obese compared to lean. Serum IL-18 was significantly higher in the PCOV groups compared to the controls and correlated directly with LAP, IR and ASCVD risk. IL-18 is elevated in PCOS patients even in lean ones and is correlated with IR and ASCVD risk.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

PubMed

Bot, Martine; de Jager, Saskia C A; MacAleese, Luke; Lagraauw, H Maxime; van Berkel, Theo J C; Quax, Paul H A; Kuiper, Johan; Heeren, Ron M A; Biessen, Erik A L; Bot, Ilze

2013-05-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.

Increased popliteal circumferential wall tension induced by orthostatic body posture is associated with local atherosclerotic plaques.

PubMed

Gemignani, Tiago; Azevedo, Renata C; Higa, Celina M; Coelho, Otávio R; Matos-Souza, José R; Nadruz, Wilson

2012-09-01

Lower limb arteries are exposed to higher hemodynamic burden in erectile posture. This study evaluated the effects of body posture on popliteal, carotid and brachial circumferential wall tension (CWT) and investigated the relationship between local CWT and atherosclerotic plaques in subjects with cardiovascular risk factors. Two hundred and three subjects (118 women and 85 men) with cardiovascular risk factors (smoking, hypertension or diabetes mellitus) underwent clinical and laboratory analysis and had their blood pressure measured in the arm and calf in supine and orthostatic positions. Arteries were evaluated by ultrasound analysis, while CWT was calculated according to Laplace's law. Among the enrolled participants, 47%, 29% and none presented popliteal, carotid and brachial plaques, respectively. Carotid CWT measurements were not associated with local plaques after adjustment for potential confounders. Conversely, general linear model and logistic regression analyses adjusted for potential confounders demonstrated that peak orthostatic CWT was the only local hemodynamic parameter showing significant relationship with popliteal plaques in the whole sample. In gender-specific analyses, although positively correlated with popliteal plaques in both genders, local peak orthostatic CWT exhibited an independent association with popliteal plaques after adjustment for potential confounders only in women. Popliteal CWT measured in orthostatic posture, rather than in supine position, is associated with popliteal atherosclerotic plaques, particularly in women. These findings suggest that erectile posture might play a role in the atherogenesis of leg arteries by modifying local hemodynamic forces and that there may be gender differences in this regard. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Control of Risk Factors for Cardiovascular Disease among Multinational Patient Population in the Arabian Gulf

PubMed Central

Al-Zakwani, Ibrahim; Al-Mahmeed, Wael; Arafah, Mohamed; Al-Hinai, Ali T.; Shehab, Abdullah; Al-Tamimi, Omer; Al-Awadhi, Mahmoud; Al-Herz, Shorook; Al-Anazi, Faisal; Al-Nemer, Khalid; Metwally, Othman; Al-Khadra, Akram; Fakhry, Mohammed; Elghetany, Hossam; Medani, Abdel R.; Yusufali, Afzal H.; Al-Jassim, Obaid; Al-Hallaq, Omar; Baslaib, Fahad O.A.S.; Amin, Haitham; Santos, Raul D.; Al-Waili, Khalid; Al-Hashmi, Khamis; Al-Rasadi, Khalid

2016-01-01

We evaluated the control of cardiovascular disease (CVD) risk factors among patients with atherosclerotic cardiovascular disease (ASCVD) in the Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolaemia (CEPHEUS) in the Arabian Gulf. Of the 4398 enrolled patients, overall mean age was 57 ± 11 years, 60% were males, 13% were smokers, 76% had diabetes, 71% had metabolic syndrome and 78% had very high ASCVD risk status. The proportion of subjects with body mass index <25 kg/m2, HbA1c <7% (in diabetics), low-density lipoprotein cholesterol (LDL-C) <2.6 mmol/L (100 mg/dL) and <1.8 mmol/L (70 mg/dL) for high and very high ASCVD risk cohorts, respectively and controlled blood pressure (<140/90 mmHg) was 14, 26, 31% and 60%, respectively. Only 1.4% of the participants had all of their CVD risk factors controlled with significant differences among the countries (P < .001). CVD risk goal attainment rates were significantly lower in those with very high ASCVD risk compared with those with high ASCVD risk status (P < .001). Females were also, generally, less likely to attain goals when compared with males (P < .001). PMID:26496982

From anatomy to function: diagnosis of atherosclerotic renal artery stenosis.

PubMed

Odudu, Aghogho; Vassallo, Diana; Kalra, Philip A

2015-12-01

Atherosclerotic renal artery stenosis (ARAS) affects 7% of the over 65 s and will be increasingly common with an ageing population. ARAS obstructs normal renal perfusion with adverse renal and cardiovascular consequences. Drug therapy is directed at reducing atherosclerotic risk. Two recent major trials of revascularization for ARAS showed that clinical outcomes were not improved beyond those offered by optimal drug therapy in most patients. This reflects experimental data showing that restoration of blood flow alone may not attenuate a cascade of tissue injury. A shift from anatomic to functional imaging of ARAS coupled to novel therapies might improve clinical outcomes in selected patients. This review outlines the case for separately assessing hemodynamic significance of arterial stenosis and functional reserve of renal parenchymal tissue. The authors consider current and emerging diagnostic techniques for ARAS and their potential to allow individualized and functionally directed treatments.

Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease.

PubMed

Gryka, Rebecca J; Buckley, Leo F; Anderson, Sarah M

2017-03-01

Despite the current standard of care, patients with cardiovascular disease remain at a high risk for recurrent events. Inhibition of thrombin-mediated platelet activation through protease-activated receptor-1 antagonism may provide reductions in atherosclerotic disease beyond those achievable with the current standard of care. Our primary objective is to evaluate the clinical literature regarding the role of vorapaxar (Zontivity™) in the reduction of cardiovascular events in patients with a history of myocardial infarction and peripheral artery disease. In particular, we focus on the potential future directions for protease-activating receptor antagonists in the treatment of a broad range of atherosclerotic diseases. A literature search of PubMed and EBSCO was conducted to identify randomized clinical trials from August 2005 to June 2016 using the search terms: 'vorapaxar', 'SCH 530348', 'protease-activated receptor-1 antagonist', and 'Zontivity™'. Bibliographies were searched and additional resources were obtained. Vorapaxar is a first-in-class, protease-activated receptor-1 antagonist. The Thrombin Receptor Antagonist for Clinical Event Reduction (TRACER) trial did not demonstrate a significant reduction in a broad primary composite endpoint. However, the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P-TIMI 50) trial examined a more traditional composite endpoint and found a significant benefit with vorapaxar. Vorapaxar significantly increased bleeding compared with standard care. Ongoing trials will help define the role of vorapaxar in patients with peripheral arterial disease, patients with diabetes mellitus, and other important subgroups. The use of multivariate modeling may enable the identification of subgroups with maximal benefit and minimal harm from vorapaxar. Vorapaxar provides clinicians with a novel mechanism of action to further reduce the burden of ischemic heart disease. Identification of

Elevated lipoprotein(a) levels are associated with coronary artery calcium scores in asymptomatic individuals with a family history of premature atherosclerotic cardiovascular disease.

PubMed

Verweij, Simone L; de Ronde, Maurice W J; Verbeek, Rutger; Boekholdt, S Matthijs; Planken, R Nils; Stroes, Erik S G; Pinto-Sietsma, Sara-Joan

2018-02-16

Elevated lipoprotein(a) (Lp(a)) levels are associated with increased risk for atherosclerotic cardiovascular disease (ASCVD). Individuals with a family history of premature ASCVD are at increased cardiovascular risk with concomitantly a higher burden of (subclinical) atherosclerosis. However, whether Lp(a) contributes to the increased atherosclerotic burden in these individuals remains to be established. In this study, we evaluated the association between Lp(a) levels and coronary atherosclerotic burden, assessed by coronary arterty calcium (CAC) scores, in asymptomatic individuals with a family history of premature ASCVD. Lp(a) levels and other ASCVD risk factors were assessed in 432 individuals with premature ASCVD and in 937 healthy asymptomatic family members. CAC scores were only measured in asymptomatic family members. In this cohort, 16% had elevated Lp(a) levels, defined as ≥ 50 mg/dL. Among healthy family members, elevated Lp(a) levels were associated with both absolute CAC scores of ≥ 100 (odds ratio [OR] 1.79 [95% confidence interval {CI} 1.13-2.83]) as well as with age- and gender-corrected CAC scores ≥ 80th percentile (OR 1.69 [95% CI 1.14-2.50]). This coincides with a higher prevalence of cardiovascular events (OR 1.48 [95% CI 1.11-2.01]) in the whole cohort. Elevated Lp(a) levels were associated with higher CAC scores, both absolute as well as age- and gender-corrected percentiles, in individuals with a family history of premature ASCVD. These data imply that Lp(a) accelerates progression of atherosclerosis in these individuals, thereby contributing to their increased ASCVD risk. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease.

PubMed

Nörenberg, Dominik; Ebersberger, Hans U; Diederichs, Gerd; Hamm, Bernd; Botnar, René M; Makowski, Marcus R

2016-03-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism.

PubMed

Doğan, Berçem Ayçiçek; Karakılıç, Ersen; Tuna, Mazhar Müslüm; Arduç, Ayşe; Berker, Dilek; Güler, Serdar

2015-03-01

Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder. Forty-three male patients aged 30 (range: 24-39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26-39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness. The carotid intima-media thickness (P < 0·001) was higher and the brachial flow-mediated diameter (P = 0·002) was lower in patients with idiopathic hypogonadotropic hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = -0·556, P = <0·001). The carotid intima-media thickness and per cent flow-mediated diameter were significantly improved in the patient group 6 months after the androgen replacement therapy (P = 0·002 and 0·026, respectively). This study indicated that low total testosterone levels can be considered a significant marker of atherosclerosis in patients with idiopathic hypogonadotropic hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months. © 2014 John Wiley & Sons Ltd.

The community pharmacist's role in reducing CVD risk factors in Lebanon: a cross-sectional longitudinal study.

PubMed

Fahs, Iqbal; Hallit, Souheil; Rahal, Mohamad; Malaeb, Diana

2018-06-13

To assess the role of pharmacist in modifying CVDs risk factors among Lebanese adults in urban and rural areas.
Materials (Subjects) and Methods
In a prospective survey, 865 out of 1000 participants aged ≥ 45, previously interviewed, agreed to be followed at 1 and 2 year time points. Parameters including blood pressure, lipid profile, blood glucose, average number of risk factors, and atherosclerotic cardiovascular disease (ASCVD) risk were assessed and evaluated at the beginning of the study, then after 1 and 2 years.
Results:
After patient's education and during both follow ups, the mean average body mass index (BMI) and systolic blood pressure (SBP) statistically decreased significantly. The lipid profile as well statistically improved significantly during both follow-ups. to around 9%. Further statistically significant improvements in ASCVD risk occurred during the second follow-up to around 8%. Monitoring parameters revealed statistical significant improvements as well.
Conclusion:
This study showed that a plan that includes pharmacists, who regularly monitor and follow-up patients, could improve CVD prevention through reduction of risk factors.
. ©2018The Author(s). Published by S. Karger AG, Basel.

Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS?

PubMed

Dursun, Polat; Demirtaş, Ezgi; Bayrak, Ahmet; Yarali, Hakan

2006-01-01

Patients with polycystic ovary syndrome (PCOS) may have an increased risk for the development of hypertension and atherosclerotic heart disease (AHD), the pathophysiological mechanisms of which are not clear. Paraoxonase1 (PON1) is a high-density lipoprotein-associated enzyme that prevents oxidative modification of low-density lipoprotein. The aim of this study was to measure the serum levels of PON1 activity in patients with PCOS and to compare with those of regularly cycling controls. Serum lipid parameters, malondialdehyde (MDA) levels and PON1 activity, were measured in PCOS patients (n = 23) and regularly cycling, age-, body mass index- and smoking status-matched controls (n = 23). All patients had normal glucose tolerance test as assessed by a 75 g oral glucose tolerance test. None of the patients had clinically evident hypertension or AHD. Apart from the mean serum PON1 activity, all parameters in the lipid profile including serum MDA levels were comparable between the two groups. There were no significant differences in respect to fasting glucose (4.64 +/- 0.5 versus 4.43 +/- 0.83 mmol/l) and fasting glucose insulin ratio (11.06 +/- 8.26 versus 11.49 +/- 4.90) among the two groups (P > 0.05). However, HOMA insulin resistance index was significantly higher in patients with PCOS compared with the controls (2.06 +/- 0.86 versus 1.51 +/- 0.49; P = 0.01). Also, mean serum PON1 activity was significantly lower in the PCOS group compared with the controls (151.2 +/- 90.8 versus 217.7 +/- 101.6, respectively; P = 0.027). Reduced serum PON1 activity might contribute to the increased susceptibility for the development of AHD in women with PCOS.

Ultrafast laser ablation for targeted atherosclerotic plaque removal

NASA Astrophysics Data System (ADS)

Lanvin, Thomas; Conkey, Donald B.; Descloux, Laurent; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

2015-07-01

Coronary artery disease, the main cause of heart disease, develops as immune cells and lipids accumulate into plaques within the coronary arterial wall. As a plaque grows, the tissue layer (fibrous cap) separating it from the blood flow becomes thinner and increasingly susceptible to rupturing and causing a potentially lethal thrombosis. The stabilization and/or treatment of atherosclerotic plaque is required to prevent rupturing and remains an unsolved medical problem. Here we show for the first time targeted, subsurface ablation of atherosclerotic plaque using ultrafast laser pulses. Excised atherosclerotic mouse aortas were ablated with ultrafast near-infrared (NIR) laser pulses. The physical damage was characterized with histological sections of the ablated atherosclerotic arteries from six different mice. The ultrafast ablation system was integrated with optical coherence tomography (OCT) imaging for plaque-specific targeting and monitoring of the resulting ablation volume. We find that ultrafast ablation of plaque just below the surface is possible without causing damage to the fibrous cap, which indicates the potential use of ultrafast ablation for subsurface atherosclerotic plaque removal. We further demonstrate ex vivo subsurface ablation of a plaque volume through a catheter device with the high-energy ultrafast pulse delivered via hollow-core photonic crystal fiber.

Addition of a novel, protective family history category allows better profiling of cardiovascular risk and atherosclerotic burden in the general population. The Asklepios Study.

PubMed

Van daele, Caroline M; De Meyer, Tim; De Buyzere, Marc L; Gillebert, Thierry C; Denil, Simon L I J; Bekaert, Sofie; Chirinos, Julio A; Segers, Patrick; De Backer, Guy G; De Bacquer, Dirk; Rietzschel, Ernst R

2013-01-01

Whereas the importance of family history (FH) is widely recognized in cardiovascular risk assessment, its full potential could be underutilized, when applied with its current simple guidelines-based definition (cFH): presence of premature cardiovascular disease (CVD) in a first-degree relative. We tested the added value of a new, extended family history definition (eFH), also taking into account later onset of disease, second-degree relatives and number of affected relatives, on profiling cardiovascular risk and atherosclerotic burden in the general population. Longitudinal population study. Random, representative population sample from Erpe-Mere and Nieuwerkerken (Belgium, primary care). 2524 male/female volunteers, aged 35-55 years, free from overt CVD. Subjects were extensively phenotyped including presence of atherosclerosis (ultrasound) and a newly developed FH questionnaire (4 generations). Compared to cFH, eFH was superior in predicting an adverse risk profile (glycemic state, elevated blood pressure, lipid abnormalities, presence of metabolic syndrome components) and presence of atherosclerosis (all age & sex-adjusted p<0.05). Unlike cFH, eFH remained a significant predictor of subclinical atherosclerosis after adjusting for confounders. Most relations with eFH were not graded but showed clear informational breakpoints, with absence of CVD (including late onset) in any first-degree relative being a negative predictor of atherosclerosis, and a particularly interesting phenotype for further study. A novel, extended FH definition is superior to the conventional definition in profiling cardiovascular risk and atherosclerotic burden in the general population. There remain clear opportunities to refine and increase the performance and informational content of this simple, readily-available inexpensive tool.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation[S

PubMed Central

Bot, Martine; de Jager, Saskia C. A.; MacAleese, Luke; Lagraauw, H. Maxime; van Berkel, Theo J. C.; Quax, Paul H. A.; Kuiper, Johan; Heeren, Ron M. A.; Biessen, Erik A. L.; Bot, Ilze

2013-01-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability. PMID:23396975

[Is regression of atherosclerotic plaque possible?

PubMed

Páramo, José A; Civeira, Fernando

As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion ('angiographic paradox'). A number of imaging modalities (vascular ultrasound and virtual histology, MRI, optical coherence tomography, positron tomography, etc.) are used for non-invasive assessment of atherosclerosis; most of them can identify plaque volume and composition beyond lumen stenosis. An 'aggressive' lipid-lowering strategy is able to reduce the plaque burden and the incidence of cardiovascular events; this may be attributable, at least in part, to plaque-stabilizing effects. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk: a comparison of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines with the 2014 National Lipid Association recommendations for patient-centered management of dyslipidemia.

PubMed

Adhyaru, Bhavin B; Jacobson, Terry A

2015-05-01

This review discusses the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults and compares it with the 2014 National Lipid Association (NLA) Recommendations for Patient-Centered Management of Dyslipidemia. The review discusses some of the distinctions between the guidelines, including how to determine a patient's atherosclerotic cardiovascular disease risk, the role of lipoprotein treatment targets, the importance of moderate- and high-intensity statin therapy, and the use of nonstatin therapy in light of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial. Copyright © 2015 Elsevier Inc. All rights reserved.

The roles of a novel anti-inflammatory factor, milk fat globule-epidermal growth factor 8, in patients with coronary atherosclerotic heart disease.

PubMed

Dai, Wen; Li, Yan; Lv, Yong-nan; Wei, Chuan-dong; Zheng, Hong-yun

2014-04-01

Inflammation is now considered a main pathogenic factor in coronary atherosclerotic heart disease (CHD), and it has a positive correlation with plaque vulnerability. A novel anti-inflammatory factor, milk fat globule-epidermal growth factor 8 (MFG-E8), has been reported as having prominent anti-inflammatory effects in sepsis. However, few studies have reported on the association between MFG-E8 and CHD. In the present study, we aimed to investigate the serum MFG-E8 concentrations in patients with different stages of CHD or without CHD. Then, we studied the associations among MFG-E8, Gensini score, and high-sensitivity C-reactive protein (hs-CRP) in Chinese patients with CHD to illustrate the role of MFG-E8 in CHD. A total of 176 controls and 295 patients with CHD were selected for this study. To evaluate CHD severity, we calculated the Gensini score for all of the subjects. Serum levels of MFG-E8 were determined by an enzyme-linked immunosorbent assay (ELISA) kit; serum total cholesterol (TC), high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c), triglyceride (TG), and hs-CRP were detected by an automatic biochemistry analyzer; and fibrinogen (FIB) was analyzed with an automatic coagulation analyzer. Compared with the controls, the CHD group had a lower level of MFG-E8 (673.20±112.34 ng/mL vs. 134.89±4.74 ng/mL, p<0.001). The level of serum MFG-E8 in the acute myocardial infarction group (118.07±10.10 ng/mL) was significantly less than that in the stable angina group (p=0.025). Further analysis showed that MFG-E8 had a negative association with the Gensini score and the hs-CRP level (r=-0.590, p<0.001; r=-0.105, p=0.022, respectively). In addition, multiple regression analysis of the association between MFG-E8 and the main cardiovascular risk factors in our cases showed that MFG-E8 had a negative association with hs-CRP and a positive association with LDL-c (all p<0.05). The serum level of MFG-E8 was negatively associated with

Secular trends in ischemic stroke subtypes and stroke risk factors.

PubMed

Bogiatzi, Chrysi; Hackam, Daniel G; McLeod, A Ian; Spence, J David

2014-11-01

Early diagnosis and treatment of a stroke improves patient outcomes, and knowledge of the cause of the initial event is crucial to identification of the appropriate therapy to maximally reduce risk of recurrence. Assumptions based on historical frequency of ischemic subtypes may need revision if stroke subtypes are changing as a result of recent changes in therapy, such as increased use of statins. We analyzed secular trends in stroke risk factors and ischemic stroke subtypes among patients with transient ischemic attack or minor or moderate stroke referred to an urgent transient ischemic attack clinic from 2002 to 2012. There was a significant decline in low-density lipoprotein cholesterol and blood pressure, associated with a significant decline in large artery stroke and small vessel stroke. The proportion of cardioembolic stroke increased from 26% in 2002 to 56% in 2012 (P<0.05 for trend). Trends remained significant after adjusting for population change. With more intensive medical management in the community, a significant decrease in atherosclerotic risk factors was observed, with a significant decline in stroke/transient ischemic attack caused by large artery atherosclerosis and small vessel disease. As a result, cardioembolic stroke/transient ischemic attack has increased significantly. Our findings suggest that more intensive investigation for cardiac sources of embolism and greater use of anticoagulation may be warranted. © 2014 American Heart Association, Inc.

Evaluation of the Obesity Genes FTO and MC4R for Contribution to the Risk of Large Artery Atherosclerotic Stroke in a Chinese Population

PubMed Central

Song, Zhi; Qiu, Lingling; Hu, Zhongyang; Liu, Jia; Liu, Ding; Hou, Deren

2016-01-01

Background Obesity is a well-established risk factor for large artery atherosclerotic (LAA) stroke. The aim of the study was to explore whether obesity genes, such as MC4R and FTO, contribute to LAA stroke risk in the Chinese Han population. Methods 322 LAA stroke patients and 473 controls were recruited. Gene polymorphism of MC4R (rs17782313) and FTO (rs8050136 and rs9939609) were genotyped. Results No differences were observed in genotype frequencies of variants of FTO (rs8050136 and rs9939609) or MC4R (rs17782313) between LAA stroke patients and control subjects. However, rs17782313 of the MC4R gene was associated with LAA stroke susceptibility in smokers (rs17782313: p = 0.020, OR (95s% CI) = 1.55 (1.07–2.23)) in the stratified analysis. Furthermore, multifactor dimensionality reduction analysis revealed that the combination of MC4R variant (rs17782313), hypertension and smoking habit was significantly associated with increased risk of LAA stroke (p < 0.0001, OR (95s% CI) = 6.57 (4.79–9.01)). Conclusion Our study indicated that the synergistic effects of MC4R variants, hypertension, and smoking habit contribute significantly to the risk of LAA stroke in the Chinese Han population. The finding revealed that obesity gene MC4R contribute to the risk of LAA stroke via a synergistic mechanism, which will provide new insight into the genetic architecture of LAA stroke. PMID:27701175

Evaluation of the Obesity Genes FTO and MC4R for Contribution to the Risk of Large Artery Atherosclerotic Stroke in a Chinese Population.

PubMed

Song, Zhi; Qiu, Lingling; Hu, Zhongyang; Liu, Jia; Liu, Ding; Hou, Deren

2016-01-01

Obesity is a well-established risk factor for large artery atherosclerotic (LAA) stroke. The aim of the study was to explore whether obesity genes, such as MC4R and FTO, contribute to LAA stroke risk in the Chinese Han population. 322 LAA stroke patients and 473 controls were recruited. Gene polymorphism of MC4R (rs17782313) and FTO (rs8050136 and rs9939609) were genotyped. No differences were observed in genotype frequencies of variants of FTO (rs8050136 and rs9939609) or MC4R (rs17782313) between LAA stroke patients and control subjects. However, rs17782313 of the MC4R gene was associated with LAA stroke susceptibility in smokers (rs17782313: p = 0.020, OR (95% CI) = 1.55 (1.07-2.23)) in the stratified analysis. Furthermore, multifactor dimensionality reduction analysis revealed that the combination of MC4R variant (rs17782313), hypertension and smoking habit was significantly associated with increased risk of LAA stroke (p < 0.0001, OR (95% CI) = 6.57 (4.79-9.01)). Our study indicated that the synergistic effects of MC4R variants, hypertension, and smoking habit contribute significantly to the risk of LAA stroke in the Chinese Han population. The finding revealed that obesity gene MC4R contribute to the risk of LAA stroke via a synergistic mechanism, which will provide new insight into the genetic architecture of LAA stroke. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

Computational Hemodynamic Analysis for the Diagnosis of Atherosclerotic Changes in Intracranial Aneurysms: A Proof-of-Concept Study Using 3 Cases Harboring Atherosclerotic and Nonatherosclerotic Aneurysms Simultaneously

PubMed Central

Endo, Hidenori; Niizuma, Kuniyasu; Endo, Toshiki; Funamoto, Kenichi; Ohta, Makoto; Tominaga, Teiji

2016-01-01

This was a proof-of-concept computational fluid dynamics (CFD) study designed to identify atherosclerotic changes in intracranial aneurysms. We selected 3 patients with multiple unruptured aneurysms including at least one with atherosclerotic changes and investigated whether an image-based CFD study could provide useful information for discriminating the atherosclerotic aneurysms. Patient-specific geometries were constructed from three-dimensional data obtained using rotational angiography. Transient simulations were conducted under patient-specific inlet flow rates measured by phase-contrast magnetic resonance velocimetry. In the postanalyses, we calculated time-averaged wall shear stress (WSS), oscillatory shear index, and relative residence time (RRT). The volume of blood flow entering aneurysms through the neck and the mean velocity of blood flow inside aneurysms were examined. We applied the age-of-fluid method to quantitatively assess the residence of blood inside aneurysms. Atherosclerotic changes coincided with regions exposed to disturbed blood flow, as indicated by low WSS and long RRT. Blood entered aneurysms in phase with inlet flow rates. The mean velocities of blood inside atherosclerotic aneurysms were lower than those inside nonatherosclerotic aneurysms. Blood in atherosclerotic aneurysms was older than that in nonatherosclerotic aneurysms, especially near the wall. This proof-of-concept study demonstrated that CFD analysis provided detailed information on the exchange and residence of blood that is useful for the diagnosis of atherosclerotic changes in intracranial aneurysms. PMID:27703491

A computational evaluation of sedentary lifestyle effects on carotid hemodynamics and atherosclerotic events incidence.

PubMed

Caruso, Maria Vittoria; Serra, Raffaele; Perri, Paolo; Buffone, Gianluca; Caliò, Francesco Giuseppe; DE Franciscis, Stefano; Fragomeni, Fragomeni

2017-01-01

Hemodynamics has a key role in atheropathogenesis. Indeed, atherosclerotic phenomena occur in vessels characterized by complex geometry and flow pattern, like the carotid bifurcation. Moreover, lifestyle is a significant risk factor. The aim of this study is to evaluate the hemodynamic effects due to two sedentary lifestyles - sitting and standing positions - in the carotid bifurcation in order to identify the worst condition and to investigate the atherosclerosis incidence. The computational fluid dynamics (CFD) was chosen to carry out the analysis, in which in vivo non-invasive measurements were used as boundary conditions. Furthermore, to compare the two conditions, one patient-specific 3D model of a carotid bifurcation was reconstructed starting from computer tomography. Different mechanical indicators, correlated with atherosclerosis incidence, were calculated in addition to flow pattern and pressure distribution: the time average wall shear stress (TAWSS), the oscillatory shear index (OSI) and the relative residence time (RRT). The results showed that the bulb and the external carotid artery emergence are the most probable regions in which atherosclerotic events could happen. Indeed, low velocity and WSS values, high OSI and, as a consequence, areas with chaotic-swirling flow, with stasis (high RRT), occur. Moreover, the sitting position is the worst condition: considering a cardiac cycle, TAWSS is less than 17.2% and OSI and RRT are greater than 17.5% and 21.2%, respectively. This study suggests that if a person spends much time in the sitting position, a high risk of plaque formation and, consequently, of stenosis could happen.

A Review on Atherosclerotic Biology, Wall Stiffness, Physics of Elasticity, and Its Ultrasound-Based Measurement.

PubMed

Patel, Anoop K; Suri, Harman S; Singh, Jaskaran; Kumar, Dinesh; Shafique, Shoaib; Nicolaides, Andrew; Jain, Sanjay K; Saba, Luca; Gupta, Ajay; Laird, John R; Giannopoulos, Argiris; Suri, Jasjit S

2016-12-01

Functional and structural changes in the common carotid artery are biomarkers for cardiovascular risk. Current methods for measuring functional changes include pulse wave velocity, compliance, distensibility, strain, stress, stiffness, and elasticity derived from arterial waveforms. The review is focused on the ultrasound-based carotid artery elasticity and stiffness measurements covering the physics of elasticity and linking it to biological evolution of arterial stiffness. The paper also presents evolution of plaque with a focus on the pathophysiologic cascade leading to arterial hardening. Using the concept of strain, and image-based elasticity, the paper then reviews the lumen diameter and carotid intima-media thickness measurements in combined temporal and spatial domains. Finally, the review presents the factors which influence the understanding of atherosclerotic disease formation and cardiovascular risk including arterial stiffness, tissue morphological characteristics, and image-based elasticity measurement.

Vitamin D deficiency may be an independent risk factor for arterial disease.

PubMed

van de Luijtgaarden, K M; Voûte, M T; Hoeks, S E; Bakker, E J; Chonchol, M; Stolker, R J; Rouwet, E V; Verhagen, H J M

2012-09-01

The aim of this study was to assess the vitamin D status in patients with occlusive or aneurysmatic arterial disease in relation to clinical cardiovascular risk profiles and markers of atherosclerotic disease. We included 490 patients with symptomatic peripheral arterial disease (PAD, n = 254) or aortic aneurysm (n = 236). Cardiovascular risk factors and comorbidities carotid intima-media thickness (CIMT), ankle-brachial index (ABI), serum high-sensitive C-reactive protein (hs-CRP) and vitamin D were assessed. Patients were categorised into severely (≤25 nmol l(-1)) or moderately (26-50 nmol l(-1)) vitamin D deficient, vitamin D insufficient (51-75 nmol l(-1)) or vitamin D sufficient (>75 nmol l(-1)). Overall, 45% of patients suffered from moderate or severe vitamin D deficiency. The prevalence of vitamin D deficiency was similar in patients with PAD and those with an aortic aneurysm. Low levels of vitamin D were associated with congestive heart failure and cerebrovascular disease. Adjusting for clinical cardiovascular risk factors, multivariable regression analyses showed that low vitamin D status was associated with higher CIMT (P = 0.001), lower ABI (P < 0.001) and higher hs-CRP (P = 0.022). The current study shows a strong association between low vitamin D status and arterial disease, independent of traditional cardiovascular risk factors and irrespective of the type of vascular disease, that is, occlusive or aneurysmatic disease. Copyright © 2012. Published by Elsevier Ltd.

Myocardial Infarction. Pathological Relevance and Relationship with Coronary Risk Factors.

PubMed

Leone, Aurelio

2017-01-01

Three types of necrosis characterize MI: coagulation necrosis, typically due to a coronarogenic mechanism, coagulative myocytolysis with formation of contract bands as an effect of sympathetic nervous system and adrenergic stimulation, and colliquative myocytolysis, characterized by myocardial fiber lysis, which is a close result of hydrolytic enzyme activity deriving from the material reaching the infarct area. Although a multifactorial etiology may be identified, nevertheless coronary alterations, which are a consequence of atherosclerotic plaque formation and complications with a reduced blood flow supply to the myocardium, are the benchmark of MI. Evidence indicates a close relationship between the MI and some coronary risk factors, associated with this pathologic pattern with a different, but high rate. Precipitating events to cause acute myocardial pathology need, however, to develop an acute myocardial infarction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cardiovascular Genetic Risk Testing for Targeting Statin Therapy in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Cost-Effectiveness Analysis.

PubMed

Jarmul, Jamie; Pletcher, Mark J; Hassmiller Lich, Kristen; Wheeler, Stephanie B; Weinberger, Morris; Avery, Christy L; Jonas, Daniel E; Earnshaw, Stephanie; Pignone, Michael

2018-04-01

It is unclear whether testing for novel risk factors, such as a cardiovascular genetic risk score (cGRS), improves clinical decision making or health outcomes when used for targeting statin initiation in the primary prevention of atherosclerotic cardiovascular disease (ASCVD). Our objective was to estimate the cost-effectiveness of cGRS testing to inform clinical decision making about statin initiation in individuals with low-to-intermediate (2.5%-7.5%) 10-year predicted risk of ASCVD. We evaluated the cost-effectiveness of testing for a 27-single-nucleotide polymorphism cGRS comparing 4 test/treat strategies: treat all, treat none, test/treat if cGRS is high, and test/treat if cGRS is intermediate or high. We tested a set of clinical scenarios of men and women, aged 45 to 65 years, with 10-year ASCVD risks between 2.5% and 7.5%. Our primary outcome measure was cost per quality-adjusted life-year gained. Under base case assumptions for statin disutility and cost, the preferred strategy is to treat all patients with ASCVD risk >2.5% without cGRS testing. For certain clinical scenarios, such as a 57-year-old man with a 10-year ASCVD risk of 7.5%, cGRS testing can be cost-effective under a limited set of assumptions; for example, when statins cost $15 per month and statin disutility is 0.013 (ie, willing to trade 3 months of life in perfect health to avoid 20 years of statin therapy), the preferred strategy (using a willingness-to-pay threshold of $50 000 per quality-adjusted life-year gained) is to test and treat if cGRS is intermediate or high. Overall, the results were not sensitive to assumptions about statin efficacy and harms. Testing for a 27-single-nucleotide polymorphism cGRS is generally not a cost-effective approach for targeting statin therapy in the primary prevention of ASCVD for low- to intermediate-risk patients. © 2018 American Heart Association, Inc.

Management and risk factor control of coronary artery disease in elderly versus nonelderly: a multicenter registry.

PubMed

Phrommintikul, Arintaya; Krittayaphong, Rungroj; Wongcharoen, Wanwarang; Boonyaratavej, Smonporn; Wongvipaporn, Chaiyasith; Tiyanon, Woraporn; Dinchuthai, Pakaphan; Kunjara-Na-Ayudhya, Rapeephon; Tatsanavivat, Pyatat; Sritara, Piyamitr

2016-12-01

Coronary artery disease (CAD) is a leading cause of death in elderly because aging is the important non-modifiable risk factors of atherosclerosis and also a predictor of poor outcomes. Underuse of guideline directed therapy may contribute to suboptimal risk factor control and worse outcomes in the elderly. We aimed to explore the management of CAD, risk factors control as well as goal attainment in elderly compared to nonelderly CAD patients. The CORE-Thailand is an ongoing multicenter, prospective, observational registry of patients with high atherosclerotic risk in Thailand. The data of 4120 CAD patients enrolled in this cohort was analyzed comparing between the elderly (age ≥ 65 years) vs. nonelderly (age < 65 years). There were 2172 elderly and 1948 nonelderly patients. The elderly CAD patients had higher prevalence of hypertension, dyslipidemia, atrial fibrillation and chronic kidney disease. The proportion of patients who received coronary revascularization was not different between the elderly and nonelderly CAD patients. Antiplatelets were prescribed less in the elderly while statin was prescribed in the similar proportion. Goal attainments of risk factor control of glycemic control, low density lipoprotein cholesterol, and smoking cessation except the blood pressure goal were higher in the elderly CAD patients. The CORE-Thailand registry showed the equity in the treatment of CAD between elderly and non-elderly. Elderly CAD patients had higher rate of goal attainment in risk factor control except blood pressure goal. The effects of goal attainment on cardiovascular outcomes will be demonstrated from ongoing cohort.

Management and Outcomes Among Chinese Hospitalized Patients With Established Cardiovascular Disease or Multiple Risk Factors.

PubMed

Yang, Jingang; Yang, Yuejin; Gu, Hongqiu; Li, Wei; Hu, Dayi

2016-02-01

We assessed the management and outcomes among hospitalized patients with coronary artery disease (CAD), stroke, peripheral artery disease (PAD), or with multiple (≥ 2) cardiovascular (CV) risk factors (multiple risk factors [MRFs]). We retrospectively studied 3732 hospitalized patients of either CV disease or ≥ 2 risk factors for atherothrombosis from October 2004 to January 2005. Outcomes included CV death, myocardial infarction (MI), stroke, and hospitalization for atherothrombotic events. About one-third had disease involving ≥ 1 vascular bed. Medication was more intense in patients with CAD than in others. The lowest use of statins and antiplatelet treatment was in the PAD-only group. Patients with PAD experienced a higher CV mortality (5.1%) than the patients with CAD (3.73%) or stroke (4.1%), P < .001. Cardiovascular death ranged from 1.2% for patients with MRFs, 2.8% for patients with 1-bed disease, 4.7% for patients with 2-bed disease to 6.4% for patients with 3-bed disease (P for trend <.001). For hospitalized patients with established atherosclerotic arterial disease, a substantial increase in CV event rates occurs with increasing numbers of affected arterial beds. Patients with PAD were at an especially high risk. © The Author(s) 2015.

Accuracy of the Atherosclerotic Cardiovascular Risk Equation in a Large Contemporary, Multiethnic Real-World Population

PubMed Central

Rana, Jamal S.; Tabada, Grace H.; Solomon, Matthew D.; Lo, Joan C.; Jaffe, Marc G.; Sung, Sue Hee; Ballantyne, Christie M.; Go, Alan S.

2016-01-01

Background The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) risk equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood. Objectives We sought to evaluate the accuracy of the 2013 ACC/AHA risk equation within a large, multiethnic population in clinical care. Methods The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels <70 or ≥190 mg/dl, prior statin use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records and ASCVD events were ascertained using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and by sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus. Results Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 Asian/Pacific Islander, and 18,745 Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk <2.50%; 0.65% for predicted risk 2.50 to 3.74%; 0.90% for predicted risk 3.75 to 4.99%; and 1.85% for predicted risk ≥5.00%, with C: 0.74. Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C: 0.68 to 0.74) was observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults with diabetes was improved, but discrimination was worse (C: 0.64). Conclusions

Intracerebral Hemorrhage Caused by Cerebral Hyperperfusion after Superficial Temporal Artery to Middle Cerebral Artery Bypass for Atherosclerotic Occlusive Cerebrovascular Disease

PubMed Central

Matano, Fumihiro; Murai, Yasuo; Mizunari, Takayuki; Adachi, Koji; Kobayashi, Shiro; Morita, Akio

Few papers have reported detailed accounts of intracerebral hemorrhage caused by cerebral hyperperfusion after superficial temporal artery to middle cerebral artery bypass (STA-MCA) bypass for atherosclerotic occlusive cerebrovascular disease. We report a case of vasogenic edema and subsequent intracerebral hemorrhage caused by the cerebral hyperperfusion syndrome (CHS) after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease disease without intense postoperative blood pressure control. A 63-year-old man with repeating left hemiparesis underwent magnetic resonance angiography (MRA), which revealed right internal carotid artery (ICA) occlusion. We performed a double bypass superficial temporal artery (STA)–middle cerebral artery (MCA) bypass surgery for the M2 and M3 branches. While the patient’s postoperative course was relatively uneventful, he suffered generalized convulsions, and computed tomography revealed a low area in the right frontal lobe on Day 4 after surgery. We considered this lesion to be pure vasogenic edema caused by cerebral hyperperfusion after revascularization. Intravenous drip infusion of a free radical scavenger (edaravone) and efforts to reduce systolic blood pressure to <120 mmHg were continued. The patient experienced severe left hemiparesis and disturbance of consciousness on Day 8 after surgery, due to intracerebral hemorrhage in the right frontal lobe at the site of the earlier vasogenic edema. Brain edema associated with cerebral hyperperfusion after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease should be recognized as a risk factor for intracerebral hemorrhage. The development of brain edema associated with CHS after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease requires not only intensive control of blood pressure, but also consideration of sedation therapy with propofol. PMID:28664022

Mechanical properties of human atherosclerotic intima tissue.

PubMed

Akyildiz, Ali C; Speelman, Lambert; Gijsen, Frank J H

2014-03-03

Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification. Copyright © 2014 Elsevier Ltd. All rights reserved.

The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

PubMed

Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

2013-11-01

Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

Atherosclerotic renovascular disease – epidemiology, treatment and current challenges

PubMed Central

Vassallo, Diana

2017-01-01

The neutral results of recent large randomized controlled trials comparing renal revascularization with optimal medical therapy in patients with atherosclerotic renovascular disease (ARVD) have cast doubt on the role of revascularization in the management of unselected patients with this condition. However, these studies have strengthened the evidence base for the role of contemporary intensive medical vascular protection therapy and aggressive risk factor control in improving clinical outcomes in ARVD. Patients presenting with ‘high-risk’ clinical features such as uncontrolled hypertension, rapidly declining renal function or flash pulmonary oedema are underrepresented in these studies; hence these results may not be applicable to all patients with ARVD. In this ‘high-risk’ subgroup, conservative management may not be sufficient in preventing adverse events, and indeed, observational evidence suggests that this specific patient subgroup may gain benefit from timely renal revascularization. Current challenges include the development of novel diagnostic techniques to establish haemodynamic significance of a stenosis, patient risk stratification and prediction of post-revascularization outcomes to ultimately facilitate patient selection for revascularization. In this paper we describe the epidemiology of this condition and discuss treatment recommendations for this condition in light of the results of recent randomized controlled trials while highlighting important clinical unmet needs and challenges faced by clinicians managing this condition. PMID:29056991

Relationship of Polycystic Ovarian Syndrome with Cardiovascular Risk Factors.

PubMed

Bilal, Muhammad; Haseeb, Abdul; Rehman, Abdur

2018-05-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. The two main documented pathogenic mechanisms are hyperinsulinemia and hyperandrogenemia but there is growing evidence for increased predisposition to cardiovascular disease, dyslipidemia, and type 2 diabetes mellitus. Our study aims to analyze the association of PCOS with cardiovascular risk factors. This is a prospective study which targeted 100 PCOS patients from Civil Hospital Karachi over a period of one year (July 2016 to July 2017). An equal number of age-matched healthy control participants were also included in the study. The student's t-test was used to assess the significance of differences using SPSS version (19). The statistical significance was set at a p-value of <.05. The most frequently presented feature associated with PCOS was primary infertility seen in 72% of the patients. Mean arterial pressure, fasting glucose and insulin levels and insulin resistance was found to be significantly different in PCOS patients as compared to their controls. A classic atherosclerotic lipid profile demonstrating elevated total cholesterol and low-density lipoprotein-C (LDL-C) levels and decreased serum high density lipoprotein-C(HDL-C) was observed in our study. This study established a significant yet independent association of PCOS with major cardiovascular risk factors. This association can effectively progress into CVD outcomes which necessitates early intervention programs and preventative strategies to reduce mortality from cardiovascular events. This study lays out the framework for conducting further researches on the PCOS women while exploring novel cardiovascular risk factors. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease.

PubMed

Bowman, Louise; Hopewell, Jemma C; Chen, Fang; Wallendszus, Karl; Stevens, William; Collins, Rory; Wiviott, Stephen D; Cannon, Christopher P; Braunwald, Eugene; Sammons, Emily; Landray, Martin J

2017-09-28

Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. Among

Progress in atherosclerotic plaque imaging

PubMed Central

Soloperto, Giulia; Casciaro, Sergio

2012-01-01

Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods. PMID:22937215

Evolution of intracranial atherosclerotic disease under modern medical therapy.

PubMed

Leung, Thomas W; Wang, Lily; Soo, Yannie O Y; Ip, Vincent H L; Chan, Anne Y Y; Au, Lisa W C; Fan, Florence S Y; Lau, Alex Y L; Leung, Howan; Abrigo, Jill; Wong, Adrian; Mok, Vincent C T; Ng, Ping Wing; Tsoi, Tak Hong; Li, Siu Hung; Man, Celeste B L; Fong, Wing Chi; Wong, Ka Sing; Yu, Simon C H

2015-03-01

Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention. In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients. Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year (p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound. A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence. © 2014 American Neurological Association.

The effect of features of the metabolic syndrome on atherosclerotic risk in relatively long-surviving patients with type 1 diabetes.

PubMed

Distiller, Larry A; Joffe, Barry I; Brown, Vanessa; Distiller, Greg B

2010-12-01

Increasing numbers of patients with type 1 diabetes (T1DM) are developing features of the metabolic syndrome. The additional effect of this on the development of atherosclerosis, as inferred by the carotid artery intima media thickness (IMT), has not previously been assessed. The aim of this study was to assess the effect of features of the metabolic syndrome on carotid artery IMT in a cohort of long-surviving patients with T1DM. Long-surviving patients with T1DM attending the Centre for Diabetes and Endocrinology were assessed regarding their risk factor profile. All underwent measurement of carotid artery IMT. In all, 156 patients who had T1DM for more than 18 years had their carotid artery IMT measured. All had been attending the clinic for over 10 years, and past clinical and laboratory records were available. A total of 37 patients had metabolic syndrome according to the International Diabetes Federation (IDF) definition. Those with metabolic syndrome had a significantly increased carotid artery IMT (P = 0.003) compared to those without the syndrome. There was a significant relationship between the number of features of metabolic syndrome and increased atherosclerotic risk according to the carotid artery IMT (P = 0.01). A significant correlation was found between carotid artery IMT and both waist circumference (P < 0.001) and insulin resistance (P = 0.005). In long-surviving patients with T1DM, those that develop metabolic syndrome are more likely to have thicker carotid artery IMT, and, by inference, be at higher risk of atherosclerosis and possibly cardiovascular disease. A linear relationship was present between both waist circumference and insulin resistance and carotid artery IMT.

Influence of ghrelin gene polymorphisms on hypertension and atherosclerotic disease.

PubMed

Berthold, Heiner K; Giannakidou, Eleni; Krone, Wilhelm; Trégouët, David-Alexandre; Gouni-Berthold, Ioanna

2010-02-01

Ghrelin is involved in several metabolic and cardiovascular processes. Recent evidence suggests its involvement in blood pressure regulation and hypertension. The aim of the study was to determine associations of single-nucleotide polymorphisms (SNPs) and haplotypes of the ghrelin gene (GHRL) with hypertension and atherosclerotic disease. Six GHRL SNPs (rs27647, rs26802, rs34911341, rs696217, rs4684677 and a -473G/A (with no assigned rsID)) were investigated in a sample of 1143 hypertensive subjects and 1489 controls of Caucasian origin. Both single-locus and haplotype association analyses were performed. In single-locus analyses, only the non-synonymous rs34911341 was associated with hypertension (odds ratio (OR)=1.95 (95% confidence interval (CI): 1.26-3.02), P=0.003). Six common haplotypes with frequency >1% were inferred from the studied GHRL SNPs, and their frequency distribution was significantly different between hypertensive subjects and controls (chi(2)=12.96 with 5 d.f. (degree of freedom), P=0.024). The effect of rs26802 was found to be significantly (P=0.017) modulated by other GHRL SNPs, as its C allele conferred either an increased risk (OR=1.30 (1.08-1.57), P=0.005) or a decreased risk (OR=0.50 (0.23-1.06), P=0.07) of hypertension according to the two different haplotypes on which it can be found. No association of GHRL SNPs or haplotypes with atherosclerotic disease was observed. In conclusion, we observed statistical evidence for association between GHRL SNPs and risk of hypertension.

αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice.

PubMed

Vancraeynest, David; Roelants, Véronique; Bouzin, Caroline; Hanin, François-Xavier; Walrand, Stephan; Bol, Vanesa; Bol, Anne; Pouleur, Anne-Catherine; Pasquet, Agnès; Gerber, Bernhard; Lesnik, Philippe; Huby, Thierry; Jamar, François; Vanoverschelde, Jean-Louis

2016-12-01

αVβ3-integrin is expressed by activated endothelial cells and macrophages in atherosclerotic plaques and may represent a valuable marker of high-risk plaques. We evaluated (99m)Tc-maraciclatide, an integrin-specific tracer, for imaging vascular inflammation in atherosclerotic lesions in mice. Apolipoprotein E-negative (ApoE(-/-)) mice on a Western diet (n = 10) and normally fed adult C57BL/6 control mice (n = 4) were injected with (99m)Tc-maraciclatide (51.8 ± 3.7 MBq). A blocking peptide was infused in three ApoE(-/-) mice; this condition served as another control. After 90 min, the animals were imaged via single-photon emission computed tomography (SPECT). While maintained in the same position, the mice were transferred to computed tomography (CT) to obtain contrast-enhanced images of the aortic arch. Images from both modalities were fused, and signal was quantified in the aortic arch and in the vena cava for subtraction of blood-pool activity. The aorta was carefully dissected after imaging for gamma counting, autoradiography, and histology. Tracer uptake was significantly higher in ApoE(-/-) mice than in both groups of control mice (1.56 ± 0.33 vs. 0.82 ± 0.24 vs. 0.98 ± 0.11, respectively; P = 0.006). Furthermore, higher tracer activity was detected via gamma counting in the aorta of hypercholesterolemic mice than in both groups of control mice (1.52 ± 0.43 vs. 0.78 ± 0.19 vs. 0.47 ± 0.31 (99m)Tc-maraciclatide %ID/g, respectively; P = 0.018). Autoradiography showed significantly higher tracer uptake in the atherosclerotic aorta than in the control aorta (P = 0.026). Finally, in the atherosclerotic aorta, immunostaining indicated that the integrin signal came predominantly from macrophages and was correlated with the macrophage CD68 immunomarker (r = 0.73). (99m)Tc-maraciclatide allows in vivo detection of inflamed atherosclerotic plaques in mice and may represent a non-invasive approach for

T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment

PubMed Central

Dong, Lei; Nordlohne, Johannes; Ge, Shuwang; Hertel, Barbara; Melk, Anette; Rong, Song; Haller, Hermann

2016-01-01

Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe−/− (apolipoprotein E) CX3CR1−/− mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor–deficient (LDLr−/−) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1−/− bone marrow into LDLr−/− mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b+CD11c+ myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1−/− splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFβ. Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFβ alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFβ induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr−/− mice, CX3CR1+/− T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1−/− T cells did not. Transfer of CX3CR1+/− but not Il17a−/− T cells into LDLr−/−CX3CR1−/− mice increased aortic lesion size and aortic CD11b+CD11c+ myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFβ and is instrumental in enhanced atherosclerosis in renal impairment. PMID:26449606

Association of socioeconomic status measured by education and risk factors for carotid atherosclerosis: cross-sectional study.

PubMed

Maksimović, Milos Z; Vlajinac, Hristina D; Radak, Dorde J; Maksimović, Jadranka M; Marinković, Jelena M; Jorga, Jagoda B

2008-12-01

To investigate the association between socioeconomic status and metabolic syndrome, lifestyle, clinical and biochemical characteristics, and inflammatory markers as risk factors for carotid atherosclerotic disease. This cross-sectional study, involving 657 consecutive patients with verified carotid atherosclerotic disease, was performed in Belgrade, Serbia, during the period 2006-2007. Formal education level was used as a proxy for socioeconomic status. Anthropometric parameters and data on cardiovascular risk factors were analyzed in participants with different levels of education--low (< or = primary school), medium (secondary school), and high (university education). In the analysis, univariate and multivariate logistic regressions were used. Multivariate analysis showed that low education was significantly positively associated with female sex (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.45-3.81), increased triglycerides (OR, 1.79; 95% CI, 1.12-2.78), increased high-sensitivity C-reactive protein (hsCRP) (OR, 3.53; 95% CI, 2.17-5.88), and physical inactivity (OR, 4.24; 95% CI, 1.82-9.86) and negatively associated with former smoking (OR, 0.42; 95% CI, 0.23-0.75). Medium education was significantly positively associated with increased triglycerides (OR, 1.73; 95% CI, 1.14-2.62) and increased hsCRP (OR, 2.17; 95% CI, 1.37-3.41), and negatively with age (OR, 0.97; 95% CI, 0.94-0.99). Increased triglycerides and hsCRP in people with low and medium education, and high prevalence of metabolic syndrome, its components and inflammatory markers in all study participants, suggest that regular health check-up, especially for those with lower education, may be useful in early detection and treatment of any abnormality that can be associated with cardiovascular disease.

CANCER BIOMARKERS IN HUMAN ATHEROSCLEROTIC LESIONS: DETECTION OF DNA ADDUCTS

EPA Science Inventory

Since somatic mutations are suspected to contribute to the pathogenesis not only of cancer but also of atherosclerotic plaques, we measured DNA adducts in the smooth muscle layer of atherosclerotic lesions in abnormal aorta specimens taken at surgery from seven patients. NA adduc...

Identification of Mature Atherosclerotic Plaque Proteome Signatures Using Data-Independent Acquisition Mass Spectrometry.

PubMed

Hansmeier, Nicole; Buttigieg, Josef; Kumar, Pankaj; Pelle, Shaneen; Choi, Kyoo Yoon; Kopriva, David; Chao, Tzu-Chiao

2018-01-05

Atherosclerosis is a chronic inflammatory disease with complex pathobiology and one of the most common causes of cardiovascular events. The process is characterized by complex vascular remodeling processes that require the actions of numerous proteins. The composition of atherosclerotic plaque is increasingly recognized as a major factor governing the occurrence of cardiovascular or neurological symptoms. To gain deeper insights into the composition of atherosclerotic plaques, we created quantitative proteome profiles of advanced plaque tissues of six male patients undergoing carotid endarterectomy for stroke prevention. Using a quantitative, data-independent proteome approach, we identified 4181 proteins with an average protein coverage of 45%. An analysis of the quantitative composition of the tissue revealed key players of vascular remodeling processes. Moreover, compared with proximal arterial tissue, 20 proteins in mature plaques were enriched, whereas 52 proteins were found in lower quantities. Among the proteins with increased abundance were prominent extracellular matrix proteins such as biglycan and lumican, whereas cytoskeletal markers for contractile smooth muscle cells (SMCs) were decreased. Taken together, this study provides the most comprehensive quantitative assessment of mature human plaque tissue to date, which indicates a central role of SMCs in the structure of advanced atherosclerotic plaques.

Are calcifying matrix vesicles in atherosclerotic lesions of cellular origin?

PubMed

Bobryshev, Yuri V; Killingsworth, Murray C; Huynh, Thuan G; Lord, Reginald S A; Grabs, Anthony J; Valenzuela, Stella M

2007-03-01

Over recent years, the role of matrix vesicles in the initial stages of arterial calcification has been recognized. Matrix calcifying vesicles have been isolated from atherosclerotic arteries and the biochemical composition of calcified vesicles has been studied. No studies have yet been carried out to examine the fine structure of matrix vesicles in order to visualize the features of the consequent stages of their calcification in arteries. In the present work, a high resolution ultrastructural analysis has been employed and the study revealed that matrix vesicles in human atherosclerotic lesions are heterogeneous with two main types which we classified. Type I calcified vesicles were presented by vesicles surrounded by two electron-dense layers and these vesicles were found to be resistant to the calcification process in atherosclerotic lesions in situ. Type II matrix vesicles were presented by vesicles surrounded by several electron-dense layers and these vesicles were found to represent calcifying vesicles in atherosclerotic lesions. To test the hypothesis that calcification of matrix vesicles surrounded by multilayer sheets may occur simply as a physicochemical process, independently from the cell regulation, we produced multilamellar liposomes and induced their calcification in vitro in a manner similar to that occurring in matrix vesicles in atherosclerotic lesions in situ.

Relationship between aortic valve calcification and the severity of coronary atherosclerotic disease.

PubMed

Qian, Juying; Chen, Zhangwei; Ge, Junbo; Ma, Jianying; Chang, Shufu; Fan, Bing; Liu, Xuebo; Ge, Lei

2010-07-01

Aortic valve calcification (AVC), which has been confirmed to be associated with various risk factors of cardiac disease, is common in the elderly and associated with increased cardiovascular mortality. It has been hypothesized that AVC is associated with coronary atherosclerotic disease, and its severity. Between July 2007 and November 2007, a total of 235 patients with chest pain or chest distress were admitted to the authors' institution for coronary angiography. The severity of coronary atherosclerotic disease (CAD) was evaluated by the Gensini score, the number of stenosed vessels, and the prevalence of total occlusion. All patients underwent transthoracic echocardiography to detect AVC. Patients with CAD had a higher prevalence of AVC than those without CAD (44% versus 26%, p = 0.005). Likewise, the prevalence of AVC was significantly higher in patients with a higher Gensini score than in those with a lower score. Patients with AVC had a higher prevalence of CAD, and higher Gensini scores and numbers of stenosed coronary arteries, even after stratification by age (65 years). On multivariable logistic regression analysis for CAD, the odds ratio (OR) of AVC was 2.315 (95% confidence interval (CI): 1.158-4.629, p = 0.018); this value was higher than that for total cholesterol (OR = 1.637, p = 0.008), lipoprotein-a (OR = 1.003, p = 0.015) and fibrinogen (OR = 1.009, p = 0.006), and marginally less than that for male gender (OR = 2.665, p = 0.005). Patients with AVC had a higher prevalence and greater severity of CAD.

Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

PubMed

Kovanen, Petri T; Bot, Ilze

2017-12-05

Mast cells are potent actors involved in inflammatory reactions in various tissues, including both in the intimal and the adventitial layers of atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast cells are activated to degranulate, and thereby triggered to release an abundance of preformed inflammatory mediators, notably histamine, heparin, neutral proteases and cytokines stored in their cytoplasmic secretory granules. Depending on the stimulus, mast cell activation may also launch prolonged synthesis and secretion of single bioactive molecules, such as cytokines and derivatives of arachidonic acid. The mast cell-derived mediators may impede the functions of different types of cells present in atherosclerotic lesions, and also compromise the structural and functional integrity of the intimal extracellular matrix. In the adventitial layer of atherosclerotic coronary arteries, mast cells locate next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may activate mast cells to release vasoactive compounds capable of triggering local vasoconstriction. The concerted actions of arterial mast cells have the potential to contribute to the initiation and progression of atherosclerosis, and ultimately to destabilization and rupture of an advanced atherosclerotic plaque with ensuing atherothrombotic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Overexpression of TGF-ß1 in Macrophages Reduces and Stabilizes Atherosclerotic Plaques in ApoE-Deficient Mice

PubMed Central

Orning, Carolin; Crain, Jeanine; Küpper, Ines; Wiese, Elena; Protschka, Martina; Blessing, Manfred; Lackner, Karl J.; Torzewski, Michael

2012-01-01

Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1) and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E) knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE−/− mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet) as indicated by aortic plaque area en face (p<0.05). Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD), significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD), significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively) without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. PMID:22829904

Healthcare resource utilization and costs in working-age patients with high-risk atherosclerotic cardiovascular disease: findings from a multi-employer claims database.

PubMed

Zhao, Z; Zhu, Y; Fang, Y; Ye, W; McCollam, P

2015-01-01

Patients with coronary artery disease with diabetes, a history of acute coronary syndromes, cerebrovascular atherosclerotic disease, or peripheral arterial disease are at particularly high risk for a cardiovascular (CV) event and can be defined as having high-risk atherosclerotic cardiovascular disease (ASCVD). The objective of this study is to examine healthcare resource utilization (HRU) and total healthcare costs (THC) for patients with ASCVD in a commercially insured population. A retrospective cohort study was conducted using a large, US employer-based, claims database. Patients with an ASCVD diagnosis between October 1, 2008 to September 30, 2009 who met eligibility requirements were included. All-cause and ASCVD-related HRU and THC for the first and second year of follow-up were examined for all patients and by the number of arterial beds affected. Adjusted THC were compared across groups with and without polyvascular disease. The analysis included 152,290 patients with ASCVD. Use of CV-related medications, hospitalizations, and office visits were highest among patients with three arterial beds affected. Mean all-cause THC for patients with ASCVD were ∼$19,000 per patient in Year 1 or Year 2, with medical costs as the main driver. ASCVD-related THC were also similar for Year 1 ($8699) and Year 2 ($7925) across all patients. Adjusted all-cause and ASCVD-related THC for both years were greatest for patients with three affected arterial beds compared with one or two affected beds (p < 0.001 for each comparison). This is the first study in a managed care setting to systematically estimate all-cause and ASCVD-related THC for an aggregated population of ASCVD patients at high risk for a CV event. The economic burden of ASCVD in working-age patients in the US is substantial. Significantly higher HRU and costs were found in patients with polyvascular disease compared with those with only one affected bed.

Discoidin Domain Receptor-1 Deficiency Attenuates Atherosclerotic Calcification and Smooth Muscle Cell-Mediated Mineralization

PubMed Central

Ahmad, Pamela J.; Trcka, Daniel; Xue, Siming; Franco, Christopher; Speer, Mei Y.; Giachelli, Cecilia M.; Bendeck, Michelle P.

2009-01-01

Intimal calcification is a feature of advanced atherosclerotic disease that predicts a two- to eightfold increase in the risk of coronary events. Type I collagen promotes vascular smooth muscle cell-mediated calcification, although the mechanism by which this occurs is unknown. The discoidin domain receptor 1 (DDR1) is a collagen receptor that is emerging as a critical mediator of atherosclerosis. To determine whether DDR1 is involved in intimal calcification, we fed male Ddr1−/−;Ldlr−/− and Ddr1+/+;Ldlr−/− mice an atherogenic diet for 6, 12, or 24 weeks. DDR1 deficiency significantly reduced the calcium content of the aortic arch, and microcomputed tomography demonstrated a significant decrease in hydroxyapatite deposition after 24 weeks of atherogenic diet. Reduced calcification was correlated with decreases in macrophage accumulation and tumor necrosis factor α staining, suggesting that the reduction in calcification was in part due to decreased inflammation. The chondrogenic markers type II collagen, type X collagen, and Sox-9 were expressed within the mineralized foci. An in vitro assay performed with vascular smooth muscle cells revealed that DDR1 was required for cell-mediated calcification of the matrix, and Ddr1+/+ smooth muscle cells expressed more alkaline phosphatase activity, whereas Ddr1−/− smooth muscle cells expressed elevated levels of mRNA for nucleotide pyrophosphatase phosphodiesterase 1, an inhibitor of tissue mineralization. Taken together, our results demonstrate that DDR1 mediates an important mechanism for atherosclerotic calcification. PMID:19893047

Discoidin domain receptor-1 deficiency attenuates atherosclerotic calcification and smooth muscle cell-mediated mineralization.

PubMed

Ahmad, Pamela J; Trcka, Daniel; Xue, Siming; Franco, Christopher; Speer, Mei Y; Giachelli, Cecilia M; Bendeck, Michelle P

2009-12-01

Intimal calcification is a feature of advanced atherosclerotic disease that predicts a two- to eightfold increase in the risk of coronary events. Type I collagen promotes vascular smooth muscle cell-mediated calcification, although the mechanism by which this occurs is unknown. The discoidin domain receptor 1 (DDR1) is a collagen receptor that is emerging as a critical mediator of atherosclerosis. To determine whether DDR1 is involved in intimal calcification, we fed male Ddr1(-/-);Ldlr(-/-) and Ddr1(+/+);Ldlr(-/-) mice an atherogenic diet for 6, 12, or 24 weeks. DDR1 deficiency significantly reduced the calcium content of the aortic arch, and microcomputed tomography demonstrated a significant decrease in hydroxyapatite deposition after 24 weeks of atherogenic diet. Reduced calcification was correlated with decreases in macrophage accumulation and tumor necrosis factor alpha staining, suggesting that the reduction in calcification was in part due to decreased inflammation. The chondrogenic markers type II collagen, type X collagen, and Sox-9 were expressed within the mineralized foci. An in vitro assay performed with vascular smooth muscle cells revealed that DDR1 was required for cell-mediated calcification of the matrix, and Ddr1(+/+) smooth muscle cells expressed more alkaline phosphatase activity, whereas Ddr1(-/-) smooth muscle cells expressed elevated levels of mRNA for nucleotide pyrophosphatase phosphodiesterase 1, an inhibitor of tissue mineralization. Taken together, our results demonstrate that DDR1 mediates an important mechanism for atherosclerotic calcification.

Association of Socioeconomic Status Measured by Education and Risk Factors for Carotid Atherosclerosis: Cross-sectional Study

PubMed Central

Maksimović, Miloš Ž.; Vlajinac, Hristina D.; Radak, Đorđe J.; Maksimović, Jadranka M.; Marinković, Jelena M.; Jorga, Jagoda B.

2008-01-01

Aim To investigate the association between socioeconomic status and metabolic syndrome, lifestyle, clinical and biochemical characteristics, and inflammatory markers as risk factors for carotid atherosclerotic disease. Methods This cross-sectional study, involving 657 consecutive patients with verified carotid atherosclerotic disease, was performed in Belgrade, Serbia, during the period 2006-2007. Formal education level was used as a proxy for socioeconomic status. Anthropometric parameters and data on cardiovascular risk factors were analyzed in participants with different levels of education – low (≤primary school), medium (secondary school), and high (university education). In the analysis, univariate and multivariate logistic regressions were used. Results Multivariate analysis showed that low education was significantly positively associated with female sex (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.45-3.81), increased triglycerides (OR, 1.79; 95% CI, 1.12-2.78), increased high-sensitivity C-reactive protein (hsCRP) (OR, 3.53; 95% CI, 2.17-5.88), and physical inactivity (OR, 4.24; 95% CI, 1.82-9.86) and negatively associated with former smoking (OR, 0.42; 95% CI, 0.23-0.75). Medium education was significantly positively associated with increased triglycerides (OR, 1.73; 95% CI, 1.14-2.62) and increased hsCRP (OR, 2.17; 95% CI, 1.37-3.41), and negatively with age (OR, 0.97; 95% CI, 0.94-0.99). Conclusion Increased triglycerides and hsCRP in people with low and medium education, and high prevalence of metabolic syndrome, its components and inflammatory markers in all study participants, suggest that regular health check-up, especially for those with lower education, may be useful in early detection and treatment of any abnormality that can be associated with cardiovascular disease. PMID:19090608

Predicting the 10-Year Risks of Atherosclerotic Cardiovascular Disease in Chinese Population: The China-PAR Project (Prediction for ASCVD Risk in China).

PubMed

Yang, Xueli; Li, Jianxin; Hu, Dongsheng; Chen, Jichun; Li, Ying; Huang, Jianfeng; Liu, Xiaoqing; Liu, Fangchao; Cao, Jie; Shen, Chong; Yu, Ling; Lu, Fanghong; Wu, Xianping; Zhao, Liancheng; Wu, Xigui; Gu, Dongfeng

2016-11-08

The accurate assessment of individual risk can be of great value to guiding and facilitating the prevention of atherosclerotic cardiovascular disease (ASCVD). However, prediction models in common use were formulated primarily in white populations. The China-PAR project (Prediction for ASCVD Risk in China) is aimed at developing and validating 10-year risk prediction equations for ASCVD from 4 contemporary Chinese cohorts. Two prospective studies followed up together with a unified protocol were used as the derivation cohort to develop 10-year ASCVD risk equations in 21 320 Chinese participants. The external validation was evaluated in 2 independent Chinese cohorts with 14 123 and 70 838 participants. Furthermore, model performance was compared with the Pooled Cohort Equations reported in the American College of Cardiology/American Heart Association guideline. Over 12 years of follow-up in the derivation cohort with 21 320 Chinese participants, 1048 subjects developed a first ASCVD event. Sex-specific equations had C statistics of 0.794 (95% confidence interval, 0.775-0.814) for men and 0.811 (95% confidence interval, 0.787-0.835) for women. The predicted rates were similar to the observed rates, as indicated by a calibration χ 2 of 13.1 for men (P=0.16) and 12.8 for women (P=0.17). Good internal and external validations of our equations were achieved in subsequent analyses. Compared with the Chinese equations, the Pooled Cohort Equations had lower C statistics and much higher calibration χ 2 values in men. Our project developed effective tools with good performance for 10-year ASCVD risk prediction among a Chinese population that will help to improve the primary prevention and management of cardiovascular disease. © 2016 American Heart Association, Inc.

Intravascular photoacoustic imaging of exogenously labeled atherosclerotic plaque through luminal blood

NASA Astrophysics Data System (ADS)

Yeager, Doug; Karpiouk, Andrei; Wang, Bo; Amirian, James; Sokolov, Konstantin; Smalling, Richard; Emelianov, Stanislav

2012-10-01

Combined intravascular ultrasound and intravascular photoacoustic (IVUS/IVPA) imaging has been previously established as a viable means for assessing atherosclerotic plaque morphological and compositional characteristics using both endogenous and exogenous contrast. In this study, IVUS/IVPA imaging of atherosclerotic rabbit aortas following systemic injection of gold nanorods (AUNRs) with peak absorbance within the tissue optical window is performed. Ex vivo imaging results reveal a high photoacoustic signal from localized AUNRs in regions with atherosclerotic plaques. Corresponding histological staining further confirms the preferential extravasation of AUNRs in atherosclerotic regions with compromised luminal endothelium and acute inflammation. The ability to detect AUNRs using combined IVUS and photoacoustic imaging in the presence of luminal saline and luminal blood is evaluated using both spectroscopic and single wavelength IVPA imaging techniques. Results demonstrate that AUNR detection within the arterial wall can be achieved using both methods, even in the case of imaging through luminal blood.

Impact of clinical input variable uncertainties on ten-year atherosclerotic cardiovascular disease risk using new pooled cohort equations.

PubMed

Gupta, Himanshu; Schiros, Chun G; Sharifov, Oleg F; Jain, Apurva; Denney, Thomas S

2016-08-31

Recently released American College of Cardiology/American Heart Association (ACC/AHA) guideline recommends the Pooled Cohort equations for evaluating atherosclerotic cardiovascular risk of individuals. The impact of the clinical input variable uncertainties on the estimates of ten-year cardiovascular risk based on ACC/AHA guidelines is not known. Using a publicly available the National Health and Nutrition Examination Survey dataset (2005-2010), we computed maximum and minimum ten-year cardiovascular risks by assuming clinically relevant variations/uncertainties in input of age (0-1 year) and ±10 % variation in total-cholesterol, high density lipoprotein- cholesterol, and systolic blood pressure and by assuming uniform distribution of the variance of each variable. We analyzed the changes in risk category compared to the actual inputs at 5 % and 7.5 % risk limits as these limits define the thresholds for consideration of drug therapy in the new guidelines. The new-pooled cohort equations for risk estimation were implemented in a custom software package. Based on our input variances, changes in risk category were possible in up to 24 % of the population cohort at both 5 % and 7.5 % risk boundary limits. This trend was consistently noted across all subgroups except in African American males where most of the cohort had ≥7.5 % baseline risk regardless of the variation in the variables. The uncertainties in the input variables can alter the risk categorization. The impact of these variances on the ten-year risk needs to be incorporated into the patient/clinician discussion and clinical decision making. Incorporating good clinical practices for the measurement of critical clinical variables and robust standardization of laboratory parameters to more stringent reference standards is extremely important for successful implementation of the new guidelines. Furthermore, ability to customize the risk calculator inputs to better represent unique clinical

Short communication: Dating components of human atherosclerotic plaques.

PubMed

Gonçalves, Isabel; Stenström, Kristina; Skog, Göran; Mattsson, Sören; Nitulescu, Mihaela; Nilsson, Jan

2010-04-02

Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied. In the present study, we determined the biological age of different components of advanced human atherosclerotic plaques by analyzing tissue levels of (14)C released into the atmosphere during the nuclear weapons tests in the late 1950s and early 1960s. Atherosclerotic plaques were obtained from 10 patients (age 46 to 80 years) undergoing carotid surgery. Different regions of the plaques were dissected and analyzed for (14)C content using accelerator mass spectrometry. At the time of surgery, the mean biological age of the cap region was 6.4+/-3.2 years, which was significantly lower than that of the shoulder region (12.9+/-3.0 years, P<0.01), the interface toward the media (12.4+/-3.3 years, P<0.01), and the core (9.8+/-4.5 years, P<0.05). Analysis of proliferative activity and rate of apoptosis showed no signs of increased cellular turnover in the cap, suggesting that the lower (14)C content reflected a more recent time of formation. These results show that the turnover time of human plaque tissue is very long and may explain why regression of atherosclerotic plaque size rarely is observed in cardiovascular intervention trials.

Accuracy of the Atherosclerotic Cardiovascular Risk Equation in a Large Contemporary, Multiethnic Population.

PubMed

Rana, Jamal S; Tabada, Grace H; Solomon, Matthew D; Lo, Joan C; Jaffe, Marc G; Sung, Sue Hee; Ballantyne, Christie M; Go, Alan S

2016-05-10

The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood. The goal of this study was to evaluate the accuracy of the 2013 ACC/AHA Pooled Cohort Risk Equation within a large, multiethnic population in clinical care. The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed up through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels <70 or ≥190 mg/dl, prior lipid-lowering therapy use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records, and ASCVD events were ascertained by using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and according to sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus. Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 were Asian/Pacific Islander, and 18,745 were Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk <2.50%; 0.65% for predicted risk 2.50% to <3.75%; 0.90% for predicted risk 3.75% to <5.00%; and 1.85% for predicted risk ≥5.00% (C statistic: 0.74). Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C statistic: 0.68 to 0.74) were observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults

Statin-centric versus low-density lipoprotein-centric approach for atherosclerotic cardiovascular disease prevention: a Singapore perspective.

PubMed

Yan, Peter; Tan, Eng Kiat Kevin; Choo, Jason Chon Jun; Liew, Choon Fong Stanley; Lau, Titus; Waters, David D

2016-07-01

The link between cholesterol levels and atherosclerotic cardiovascular disease (ASCVD) is well-established. In Singapore, there is an increasing prevalence of risk factors for ASCVD. Like many Asian countries, Singapore's population is rapidly ageing and increasingly sedentary, which predisposes individuals to chronic health problems. Current international and local guidelines recommend statin therapy for the primary and secondary prevention of ASCVD. However, despite the effectiveness of statin therapy, some studies have highlighted that Asian patients with cardiovascular disease are not achieving target lipid goals. Furthermore, it is widely believed that the responses of Asians (both patients and physicians) to statin therapy are different from those of their Western counterparts. Experts convened in 2014 to determine the impact of current guidelines on clinical practice in Singapore. This review summarises the key findings and recommendations of these guidelines, and presents key principles to aid clinicians to manage the cardiovascular risk of their patients more effectively. Copyright: © Singapore Medical Association.

Statin-centric versus low-density lipoprotein-centric approach for atherosclerotic cardiovascular disease prevention: a Singapore perspective

PubMed Central

Yan, Peter; Tan, Eng Kiat Kevin; Choo, Jason Chon Jun; Liew, Choon Fong Stanley; Lau, Titus; Waters, David D

2016-01-01

The link between cholesterol levels and atherosclerotic cardiovascular disease (ASCVD) is well-established. In Singapore, there is an increasing prevalence of risk factors for ASCVD. Like many Asian countries, Singapore’s population is rapidly ageing and increasingly sedentary, which predisposes individuals to chronic health problems. Current international and local guidelines recommend statin therapy for the primary and secondary prevention of ASCVD. However, despite the effectiveness of statin therapy, some studies have highlighted that Asian patients with cardiovascular disease are not achieving target lipid goals. Furthermore, it is widely believed that the responses of Asians (both patients and physicians) to statin therapy are different from those of their Western counterparts. Experts convened in 2014 to determine the impact of current guidelines on clinical practice in Singapore. This review summarises the key findings and recommendations of these guidelines, and presents key principles to aid clinicians to manage the cardiovascular risk of their patients more effectively. PMID:27439304

Myeloperoxidase-oxidized high density lipoprotein impairs atherosclerotic plaque stability by inhibiting smooth muscle cell migration.

PubMed

Zhou, Boda; Zu, Lingyun; Chen, Yong; Zheng, Xilong; Wang, Yuhui; Pan, Bing; Dong, Min; Zhou, Enchen; Zhao, Mingming; Zhang, Youyi; Zheng, Lemin; Gao, Wei

2017-01-10

High density lipoprotein (HDL) has been proved to be a protective factor for coronary heart disease. Notably, HDL in atherosclerotic plaques can be nitrated (NO 2 -oxHDL) and chlorinated (Cl-oxHDL) by myeloperoxidase (MPO), likely compromising its cardiovascular protective effects. Here we determined the effects of NO 2 -oxHDL and Cl-oxHDL on SMC migration using wound healing and transwell assays, proliferation using MTT and BrdU assays, and apoptosis using Annexin-V assay in vitro, as well as on atherosclerotic plaque stability in vivo using a coratid artery collar implantation mice model. Our results showed that native HDL promoted SMC proliferation and migration, whereas NO 2 -oxHDL and Cl-oxHDL inhibited SMC migration and reduced capacity of stimulating SMC proliferation as well as migration, respectively. OxHDL had no significant influence on SMC apoptosis. In addition, we found that ERK1/2-phosphorylation was significantly lower when SMCs were incubated with NO 2 -oxHDL and Cl-oxHDL. Furthermore, transwell experiments showed that differences between native HDL, NO 2 -oxHDL and Cl-oxHDL was abolished after PD98059 (MAPK kinase inhibitor) treatment. In aortic SMCs from scavenger receptor BI (SR-BI) deficient mice, differences between migration of native HDL, NO 2 -oxHDL and Cl-oxHDL treated SMCs vanished, indicating SR-BI's possible role in HDL-associated SMC migration. Importantly, NO 2 -oxHDL and Cl-oxHDL induced neointima formation and reduced SMC positive staining cells in atherosclerotic plaque, resulting in elevated vulnerable index of atherosclerotic plaque. These findings implicate MPO-catalyzed oxidization of HDL may contribute to atherosclerotic plaque instability by inhibiting SMC proliferation and migration through MAPK-ERK pathway which was dependent on SR-BI.

Potential Anti-Atherosclerotic Properties of Astaxanthin.

PubMed

Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

2016-02-05

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed.

Potential Anti-Atherosclerotic Properties of Astaxanthin

PubMed Central

Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

2016-01-01

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed. PMID:26861359

Dispersive aortic cannulas reduce aortic wall shear stress affecting atherosclerotic plaque embolization.

PubMed

Assmann, Alexander; Gül, Fethi; Benim, Ali Cemal; Joos, Franz; Akhyari, Payam; Lichtenberg, Artur

2015-03-01

Neurologic complications during on-pump cardiovascular surgery are often induced by mobilization of atherosclerotic plaques, which is directly related to enhanced wall shear stress. In the present study, we numerically evaluated the impact of dispersive aortic cannulas on aortic blood flow characteristics, with special regard to the resulting wall shear stress profiles. An idealized numerical model of the human aorta and its branches was created and used to model straight as well as bent dispersive aortic cannulas with meshlike tips inserted in the distal ascending aorta. Standard cannulas with straight beveled or bent tips served as controls. Using a recently optimized computing method, simulations of pulsatile and nonpulsatile extracorporeal circulation were performed. Dispersive aortic cannulas reduced the maximum and average aortic wall shear stress values to approximately 50% of those with control cannulas, while the difference in local values was even larger. Moreover, under pulsatile circulation, dispersive cannulas shortened the time period during which wall shear stress values were increased. The turbulent kinetic energy was also diminished by utilizing dispersive cannulas, reducing the risk of hemolysis. In summary, dispersive aortic cannulas decrease aortic wall shear stress and turbulence during extracorporeal circulation and may therefore reduce the risk of endothelial and blood cell damage as well as that of neurologic complications caused by atherosclerotic plaque mobilization. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity†

PubMed Central

Olson, Emilia S.; Whitney, Michael A.; Friedman, Beth; Aguilera, Todd A.; Crisp, Jessica L.; Baik, Fred M.; Jiang, Tao; Baird, Stephen M.; Tsimikas, Sotirios; Tsien, Roger Y.

2012-01-01

Thrombin and other coagulation enzymes have been shown to be important during atherosclerotic disease development. Study of these proteases is currently limited because of lack of robust molecular imaging agents for imaging protease activity in vivo. Activatable cell penetrating peptides (ACPPs) have been used to monitor MMP activity in tumors and, in principle, can be modified to detect other proteases. We have developed a probe that incorporates the peptide sequence DPRSFL from the proteinase activated receptor 1 (PAR-1) into an ACPP and shown that it is preferentially cleaved by purified thrombin. Active thrombin in serum cleaves DPRSFL–ACPP with >90% inhibition by lepirudin or argatroban. The DPRSFL–ACPP cleavage product accumulated in advanced atherosclerotic lesions in living mice, with 85% reduction in retention upon pre-injection of mice with hirudin. Uptake of the ACPP cleavage product was highest in plaques with histological features associated with more severe disease. Freshly resected human atheromas bathed in DPRSFL–ACPP retained 63% greater cleavage product compared to control ACPP. In conclusion, DPRSFL–ACPP can be used to study thrombin activity in coagulation and atherosclerosis with good spatial and temporal resolution. Thrombin-sensitive ACPPs may be developed into probes for early detection and intraoperative imaging of high risk atherosclerotic plaques. PMID:22534729

In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity.

PubMed

Olson, Emilia S; Whitney, Michael A; Friedman, Beth; Aguilera, Todd A; Crisp, Jessica L; Baik, Fred M; Jiang, Tao; Baird, Stephen M; Tsimikas, Sotirios; Tsien, Roger Y; Nguyen, Quyen T

2012-06-01

Thrombin and other coagulation enzymes have been shown to be important during atherosclerotic disease development. Study of these proteases is currently limited because of lack of robust molecular imaging agents for imaging protease activity in vivo. Activatable cell penetrating peptides (ACPPs) have been used to monitor MMP activity in tumors and, in principle, can be modified to detect other proteases. We have developed a probe that incorporates the peptide sequence DPRSFL from the proteinase activated receptor 1 (PAR-1) into an ACPP and shown that it is preferentially cleaved by purified thrombin. Active thrombin in serum cleaves DPRSFL-ACPP with >90% inhibition by lepirudin or argatroban. The DPRSFL-ACPP cleavage product accumulated in advanced atherosclerotic lesions in living mice, with 85% reduction in retention upon pre-injection of mice with hirudin. Uptake of the ACPP cleavage product was highest in plaques with histological features associated with more severe disease. Freshly resected human atheromas bathed in DPRSFL-ACPP retained 63% greater cleavage product compared to control ACPP. In conclusion, DPRSFL-ACPP can be used to study thrombin activity in coagulation and atherosclerosis with good spatial and temporal resolution. Thrombin-sensitive ACPPs may be developed into probes for early detection and intraoperative imaging of high risk atherosclerotic plaques.

Does Pomegranate intake attenuate cardiovascular risk factors in hemodialysis patients?

PubMed Central

2014-01-01

Background Atherosclerotic cardiovascular disease (CVD) is the most common cause of morbidity and mortality among hemodialysis (HD) patients. It has been attributed, among other causes, to hypertension and dyslipidemia. The aim of the present study was to investigate the effect of a year-long consumption of Pomegranate juice (PJ), on two traditional cardiovascular (CV) risk factors: hypertension and lipid profile, as well as on cardiovascular events. Methods 101 HD patients were randomized to receive 100 cc of PJ (0.7 mM polyphenols) or matching placebo juice, three times a week for one year. The primary endpoints were traditional CV risk factors; blood pressure and lipid profile. Systolic, diastolic and pulse pressure, plasma levels of triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol were monitored quarterly during the study year. Secondary endpoint was incidence of cardiovascular events. Results PJ consumption yielded a significant time response improvement in systolic blood pressure, pulse pressure, triglycerides and HDL level; an improvement that was not observed in the placebo intake group. These beneficial outcomes were more pronounced among patients with hypertension, high level of triglycerides and low levels of HDL. Conclusion Regular PJ consumption by HD patients reduced systolic blood pressure and improved lipid profile. These favorable changes may reduce the accelerated atherosclerosis and high incidence of CVD among HD patients. Trial registration ClinicalTrials.gov registry, Identifier number: NCT00727519 PMID:24593225

Vulnerable atherosclerotic plaque detection by resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Liu, Cheng-hui; Boydston-White, Susie; Weisberg, Arel; Wang, Wubao; Sordillo, Laura A.; Perotte, Adler; Tomaselli, Vincent P.; Sordillo, Peter P.; Pei, Zhe; Shi, Lingyan; Alfano, Robert R.

2016-12-01

A clear correlation has been observed between the resonance Raman (RR) spectra of plaques in the aortic tunica intimal wall of a human corpse and three states of plaque evolution: fibrolipid plaques, calcified and ossified plaques, and vulnerable atherosclerotic plaques (VPs). These three states of atherosclerotic plaque lesions demonstrated unique RR molecular fingerprints from key molecules, rendering their spectra unique with respect to one another. The vibrational modes of lipids, cholesterol, carotenoids, tryptophan and heme proteins, the amide I, II, III bands, and methyl/methylene groups from the intrinsic atherosclerotic VPs in tissues were studied. The salient outcome of the investigation was demonstrating the correlation between RR measurements of VPs and the thickness measurements of fibrous caps on VPs using standard histopathology methods, an important metric in evaluating the stability of a VP. The RR results show that VPs undergo a structural change when their caps thin to 66 μm, very close to the 65-μm empirical medical definition of a thin cap fibroatheroma plaque, the most unstable type of VP.

How to manage hypertension with atherosclerotic renal artery stenosis?

PubMed

Ricco, Jean-Baptiste; Belmonte, Romain; Illuminati, Guilio; Barral, Xavier; Schneider, Fabrice; Chavent, Bertrand

2017-04-01

The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

Psoriasis as a cardiovascular risk factor: updates and algorithmic approach.

PubMed

Cozzani, Emanuele; Rosa, Gianmarco; Burlando, Martina; Parodi, Aurora

2018-04-19

Although psoriasis is predominantly a chronic inflammatory skin disorder, it has been known to be associated with cardiovascular disease. Patients with psoriasis, particularly with moderate to severe forms, present an increased rate of cardiovascular mortality, myocardial infarction and stroke. However the pathophysiology of the relationship between psoriasis and cardiovascular risk and comorbidities has not yet completely known. Chronic inflammation may be considered a solid link between psoriasis and related cardiovascular events. Several cytokines and inflammatory cells play a pivotal role in the development of psoriatic lesions, resulting in angiogenesis and endothelial dysfunction. Furthermore, the imbalance between oxidative stress and anti-oxidant mechanisms in psoriatic patients may contribute to explain the pathogenesis of increased reactive oxygen species and the formation of atherosclerotic plaque. Other mechanistic pathways which may be involved in this relationship include cardiovascular effects of medications, a common genetic background and a higher prevalence of cardiovascular risk factors, which are often under-diagnosed and under-treated in psoriatic patients. Indeed, the early detection of specific markers of cardiovascular impairment, such as N-terminal pro B-type natriuretic peptide, homocysteine and YKL-40, may enable psoriatic patients at higher cardiovascular risk to be identified as soon as possible. This review examines the increased cardiovascular risk profile and high prevalence of cardiovascular disease associated with psoriasis, focusing on pathogenic links between psoriasis and atherosclerosis, serological markers of cardiovascular involvement and the implications of anti-psoriatic therapies on cardiovascular risk and proposes a flow chart, that every dermatologist should follow to screen psoriatic patients.

Evaluation of Selected Atherosclerosis Risk Factors in Women with Subclinical Hypothyroidism Treated with L-Thyroxine.

PubMed

Adamarczuk-Janczyszyn, Maria; Zdrojowy-Wełna, Aleksandra; Rogala, Natalia; Zatońska, Katarzyna; Bednarek-Tupikowska, Grażyna

2016-01-01

Subclinical hypothyroidism (SCH) is a common endocrine disorder, probably increasing cardiovascular (CV) risk. However, the relation between SCH and atherosclerosis risk factors remains unclear. The aim of the study was to evaluate selected atherosclerosis risk factors in women with SCH in comparison to a group of healthy women and women with overt hypothyroidism, as well as to investigate the influence of L-thyroxine replacement on those risk factors. The study group consisted of 187 obese women aged between 50 and 70 years: 100 women with SCH, 45 women with overt hypothyroidism and 42 women with TSH level in reference ranges. Anthropometric parameters were evaluated. Laboratory tests included thyroid hormones concentrations, lipid profile with apolipoproteins, CRP, homocysteine. Atherosclerotic indexes were calculated: LDL C/HDL C ratio, apoA1/apoB ratio and Castelli risk index. Women with hypothyroidism were given L-thyroxine treatment and after 6 months in euthyroidism the evaluation was repeated. Total cholesterol, LDL-cholesterol and triglycerides concentrations as well as LDL-C/HDL-C ratio and Castelli index were higher in SCH than in controls and decreased after L-thyroxin substitution. All of the calculated atherosclerosis indexes showed significant positive correlations with TSH concentration in SCH group. Also in this group the systolic and diastolic blood pressure decreased significantly after treatment. Dyslipidemia in obese SCH women is not severe, but if untreated for many years, it may lead to atherosclerosis. Substitution therapy improves the lipid profile, changing the relations between protective and proatherogenic fractions of serum lipids, and optimises blood pressure.

Related factors for worsening renal function following percutaneous transluminal renal angioplasty (PTRA) in patients with atherosclerotic renal artery stenosis.

PubMed

Yoshihara, Fumiki; Fukuda, Tetsuya; Iwashima, Yoshio; Nakamura, Satoko; Hayashi, Shin-Ichiro; Kishida, Masatsugu; Ishizuka, Azusa; Kusunoki, Hiroshi; Ohta, Yuko; Kawano, Yuhei

2015-01-01

To identify candidates for PTRA in terms of the preservation of renal function, we herein evaluated factors that caused worsening renal function (WRF) after PTRA. We evaluated 92 patients with atherosclerotic renal artery stenosis (mean age 70.7 ± 8.4 years). WRF was defined as a ≥0.3 mg/dL increase in creatinine levels after PTRA compared to before PTRA. A total of 92 patients exhibited non-WRF 83 (90.2%), WRF 9 (9.8%). Significant differences were observed in serum creatinine levels between two groups both before (non-WRF 1.34 ± 0.49 versus WRF 1.70 ± 0.68 mg/dL, p = 0.0462) and after PTRA (non-WRF 1.31 ± 0.43 versus WRF 2.42 ± 1.12 mg/dL, p < 0.0001). Patients with WRF had higher comorbidity rate of diabetes mellitus (DM) (non-WRF 31.3% versus WRF 66.7%, p = 0.0345) and proteinuria (non-WRF 27.7% versus WRF 66.7%, p = 0.0169), and had higher systolic blood pressure (non-WRF 143.6 ± 18.7 versus WRF 157.1 ± 19.9 mmHg, p = 0.0436), higher plasma B-type natriuretic peptide (BNP) levels, and larger left atrial and left ventricular end-diastolic dimensions before PTRA. Patients with WRF had a higher rate of taking diuretics (non-WRF 27.7% versus WRF 66.7%, p = 0.0169) after PTRA. Multiple logistic regression analysis revealed that comorbidity of DM was an independent related factor for WRF (comorbidity of DM, yes: OR 31.0, 95% CI 2.44-1024.62, p = 0.0055). Comorbidity of DM, coexisting of proteinuria, high creatinine level, high blood pressure, high BNP levels, and large left atrial and ventricular dimensions were related to WRF after PTRA in patients with atherosclerotic renal artery stenosis.

Alloimmune responses and atherosclerotic disease after kidney transplantation.

PubMed

Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Bisaccia, Vincent; Roubiou, Caroline; Crepin, Thomas; Gaugler, Béatrice; Laheurte, Caroline; Rebibou, Jean-Michel; Chalopin, Jean-Marc; Saas, Philippe

2015-01-01

Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57(+)CD28(-) hyperactivated CD8(+) T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients. Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5-6, 3-4, and 0-2 mismatches, respectively; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10-1.66, for each supplementary mismatch; P=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05-0.95; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57(+)CD28(-) CD8(+) T cells (R=0.31; P=0.017). These CD8(+) T cells were more frequent in patients with more HLA mismatches (P<0.0001). Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.

Seventh-Day Adventist adolescents--life-style patterns and cardiovascular risk factors.

PubMed

Cooper, R; Allen, A; Goldberg, R; Trevisan, M; Van Horn, L; Liu, K; Steinhauer, M; Rubenstein, A; Stamler, J

1984-03-01

The life-style of adolescents attending a Seventh-Day Adventist boarding school was evaluated as it related to cardiovascular risk factors. The diet contained 34% calories as fat, with 11% derived from saturated fat. Total serum cholesterol levels were low (mean, standard deviation=138+/-15 mg per dl), and apolipoprotein B level was low as well (46+/-9 mg per dl). The high-density lipoprotein cholesterol level was within the usual range (52.4+/-13.3 mg per dl). Mean blood pressures were also low (systolic, 104.1+/-9.6 mm of mercury; diastolic, 65.7+/-9.7 mm of mercury). There was no self-reported use of cigarettes. If this life-style were to continue through adulthood, the incidence of premature atherosclerotic disease, particularly coronary artery disease, for this group might well be reduced, compared with other North Americans, as suggested by findings from previous studies of adult Seventh-Day Adventists.

Seventh-Day Adventist Adolescents—Life-style Patterns and Cardiovascular Risk Factors

PubMed Central

Cooper, Richard; Allen, Arline; Goldberg, Ronald; Trevisan, Maurizio; Horn, Linda Van; Liu, Kiang; Steinhauer, Michael; Rubenstein, Arthur; Stamler, Jeremiah

1984-01-01

The life-style of adolescents attending a Seventh-Day Adventist boarding school was evaluated as it related to cardiovascular risk factors. The diet contained 34% calories as fat, with 11% derived from saturated fat. Total serum cholesterol levels were low (mean, standard deviation=138±15 mg per dl), and apolipoprotein B level was low as well (46±9 mg per dl). The high-density lipoprotein cholesterol level was within the usual range (52.4±13.3 mg per dl). Mean blood pressures were also low (systolic, 104.1±9.6 mm of mercury; diastolic, 65.7±9.7 mm of mercury). There was no self-reported use of cigarettes. If this life-style were to continue through adulthood, the incidence of premature atherosclerotic disease, particularly coronary artery disease, for this group might well be reduced, compared with other North Americans, as suggested by findings from previous studies of adult Seventh-Day Adventists. PMID:6710991

Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions

PubMed Central

Almer, Gunter; Saba-Lepek, Matthias; Haj-Yahya, Samih; Rohde, Eva; Strunk, Dirk; Fröhlich, Eleonore; Prassl, Ruth; Mangge, Harald

2011-01-01

Background: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions. Methods: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy. Results: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice. Conclusion: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions. PMID:22022204

Quantification of atherosclerotic plaque activity and vascular inflammation using [18-F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).

PubMed

Mehta, Nehal N; Torigian, Drew A; Gelfand, Joel M; Saboury, Babak; Alavi, Abass

2012-05-02

Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC) and carotid intimal medial thickness (C-IMT) provide information about the burden of disease. However, despite multiple validation studies of CAC, and C-IMT, these modalities do not accurately assess plaque characteristics, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events. [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity, an important source of cellular inflammation in vessel walls. More recently, we and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors and is also highly associated with overall burden of atherosclerosis. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy as well as longer term therapeutic lifestyle changes (16 months). The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients.

PubMed

Chhibber-Goel, Jyoti; Singhal, Varsha; Bhowmik, Debaleena; Vivek, Rahul; Parakh, Neeraj; Bhargava, Balram; Sharma, Amit

2016-01-01

Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from coronary artery disease patients. In this study, we present meta-analysis from published studies that have independently investigated the presence of bacteria within atherosclerotic plaque samples in coronary artery disease patients. Data were collated from 63 studies covering 1791 patients spread over a decade. Our analysis confirms the presence of 23 oral commensal bacteria, either individually or in co-existence, within atherosclerotic plaques in patients undergoing carotid endarterectomy, catheter-based atherectomy, or similar procedures. Of these 23 bacteria, 5 ( Campylobacter rectus , Porphyromonas gingivalis , Porphyromonas endodontalis , Prevotella intermedia , Prevotella nigrescens ) are unique to coronary plaques, while the other 18 are additionally present in non-cardiac organs, and associate with over 30 non-cardiac disorders. We have cataloged the wide spectrum of proteins secreted by above atherosclerotic plaque-associated bacteria, and discuss their possible roles during microbial migration via the bloodstream. We also highlight the prevalence of specific poly-microbial communities within atherosclerotic plaques. This work provides a resource whose immediate implication is the necessity to systematically catalog landscapes of atherosclerotic plaque-associated oral commensal bacteria in human patient populations.

64Cu-Labeled Divalent Cystine Knot Peptide for Imaging Carotid Atherosclerotic Plaques.

PubMed

Jiang, Lei; Tu, Yingfeng; Kimura, Richard H; Habte, Frezghi; Chen, Hao; Cheng, Kai; Shi, Hongcheng; Gambhir, Sanjiv Sam; Cheng, Zhen

2015-06-01

The rupture of vulnerable atherosclerotic plaques that lead to stroke and myocardial infarction may be induced by macrophage infiltration and augmented by the expression of integrin αvβ3. Indeed, atherosclerotic angiogenesis may be a promising marker of inflammation. In this study, an engineered integrin αvβ3-targeting PET probe, (64)Cu-NOTA-3-4A, derived from a divalent knottin miniprotein was evaluated in a mouse model for carotid atherosclerotic plaques. Atherosclerotic plaques in BALB/C mice, maintained on a high-fat diet, were induced with streptozotocin injection and carotid artery ligation and verified by MR imaging. Knottin 3-4A was synthesized by solid-phase peptide synthesis chemistry and coupled to 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) before radiolabeling with (64)Cu. PET probe stability in mouse serum was evaluated. Mice with carotid atherosclerotic plaques were injected via the tail vein with (64)Cu-NOTA-3-4A or (18)F-FDG, followed by small-animal PET/CT imaging at different time points. Receptor targeting specificity of the probe was verified by coinjection of c(RGDyK) administered in molar excess. Subsequently, carotid artery dissection and immunofluorescence staining were performed to evaluate target expression. (64)Cu-NOTA-3-4A was synthesized in high radiochemical purity and yield and demonstrated molecular stability in both phosphate-buffered saline and mouse serum at 4 h. Small-animal PET/CT showed that (64)Cu-NOTA-3-4A accumulated at significantly higher levels in the neovasculature of carotid atherosclerotic plaques (7.41 ± 1.44 vs. 0.67 ± 0.23 percentage injected dose/gram, P < 0.05) than healthy or normal vessels at 1 h after injection. (18)F-FDG also accumulated in atherosclerotic lesions at 0.5 and 1 h after injection but at lower plaque-to-normal tissue ratios than (64)Cu-NOTA-3-4A. For example, plaque-to-normal carotid artery ratios for (18)F-FDG and (64)Cu-NOTA-3-4A at 1 h after injection were 3.75 and 14.71 (P < 0

Risk factors associated with coronary artery calcification should be examined before kidney transplantation.

PubMed

Simic-Ogrizovic, Sanja; Bogavac-Stanojevic, Natasa; Vuckovic, Maja; Dopsaj, Violeta; Giga, Voja; Kravljaca, Milica; Stosovic, Milan; Lezaic, Visnja

2012-02-01

The best treatment for end stage renal disease (ESRD) patients is kidney transplantation, but the renal transplant recipients still have a higher incidence of cardiovascular events compared with general population. Cardiovascular risk factors were imposed long before ESRD, as the majority of patients starting dialysis or kidney transplantation already have signs of advanced atherosclerosis. Artery calcification is an organized, regulated process similar to bone formation. Coronary artery calcification (CAC) is found frequently in advanced atherosclerotic lesions and could be a useful marker of them. We evaluated the prevalence of CAC in 49 stable renal transplant recipients and in 48 age- and gender-matched patients with chronic kidney disease (CKD) in stages 2-5 not requiring dialysis to assess risk factors associated with CAC. Computed tomography was used for CAC detection and quantification (CAC score). The prevalence of CAC was 43.8% in transplant recipients and 16.7% in CKD patients (p < 0.001). Transplant recipients with CAC were significantly older and had longer duration of CKD and/or dialysis than recipients without CAC. In contrast, the serum levels of fetuin A (an inhibitor of vascular calcification) and albumin were significantly lower in CKD patients with CAC than those without CAC. During the observation period (30 months), 30 patients, including 23 CKD patients, began dialysis, and 4 transplant recipients and 2 CKD patients died. Independent predictors of mortality were age, serum amyloid A and the CAC score. In conclusion, the examination and prevention of risk factors associated with atherosclerosis should be started at the beginning of renal failure.

Near-infrared hyperspectral imaging of atherosclerotic plaque in WHHLMI rabbit artery

NASA Astrophysics Data System (ADS)

Ishii, Katsunori; Kitayabu, Akiko; Omiya, Kota; Honda, Norihiro; Awazu, Kunio

2013-03-01

Hyperspectral imaging (HSI) of rabbit atherosclerotic plaque in near-infrared (NIR) range from 1150 to 2400 nm was demonstrated. A method to identify vulnerable plaques that are likely to cause acute coronary events has been required. The object of this study is identifying vulnerable plaques by NIR-HSI for an angioscopic application. In this study, we observed the hyperspectral images of the atherosclerotic plaque in WHHLMI rabbit (atherosclerotic rabbit) artery under simulated angioscopic conditions by NIR-HSI. NIR-HSI system was constructed by a NIR super continuum light and a mercury-cadmium-telluride camera. Spectral absorbance values (log (1/R) data) were obtained in the wavelength range from 1150 to 2400 nm at 10 nm intervals. The hyperspectral images were constructed with spectral angle mapper algorithm. As a result, the detections of atherosclerotic plaque under angioscopic observation conditions were achieved especially in the wavelength around 1200 nm, which corresponds to the second overtone of CH stretching vibration mode. The NIR-HSI was considered to serve as an angioscopic diagnosis technique to identify vulnerable plaques without clamping and saline injection.

Multiple Interacting Risk Factors: On Methods for Allocating Risk Factor Interactions.

PubMed

Price, Bertram; MacNicoll, Michael

2015-05-01

A persistent problem in health risk analysis where it is known that a disease may occur as a consequence of multiple risk factors with interactions is allocating the total risk of the disease among the individual risk factors. This problem, referred to here as risk apportionment, arises in various venues, including: (i) public health management, (ii) government programs for compensating injured individuals, and (iii) litigation. Two methods have been described in the risk analysis and epidemiology literature for allocating total risk among individual risk factors. One method uses weights to allocate interactions among the individual risk factors. The other method is based on risk accounting axioms and finding an optimal and unique allocation that satisfies the axioms using a procedure borrowed from game theory. Where relative risk or attributable risk is the risk measure, we find that the game-theory-determined allocation is the same as the allocation where risk factor interactions are apportioned to individual risk factors using equal weights. Therefore, the apportionment problem becomes one of selecting a meaningful set of weights for allocating interactions among the individual risk factors. Equal weights and weights proportional to the risks of the individual risk factors are discussed. © 2015 Society for Risk Analysis.

H19, a marker of developmental transition, is reexpressed in human atherosclerotic plaques and is regulated by the insulin family of growth factors in cultured rabbit smooth muscle cells.

PubMed

Han, D K; Khaing, Z Z; Pollock, R A; Haudenschild, C C; Liau, G

1996-03-01

H19 is a developmentally regulated gene with putative tumor suppressor activity, and loss of H19 expression may be involved in Wilms' tumorigenesis. In this report, we have performed in situ hybridization analysis of H19 expression during normal rabbit development and in human atherosclerotic plaques. We have also used cultured smooth muscle cells to identify H19 regulatory factors. Our data indicate that H19 expression in the developing skeletal and smooth muscles correlated with specific differentiation events in these tissues. Expression of H19 in the skeletal muscle correlated with nonproliferative, actin-positive muscle cells. In the prenatal blood vessel, H19 expression was both temporally and spatially regulated with initial loss of expression in the inner smooth muscle layers adjacent to the lumen. We also identified H19-positive cells within the adult atherosclerotic lesion and we suggest that these cells may recapitulate earlier developmental events. These results, along with the identification of the insulin family of growth factors as potent regulatory molecules for H19 expression, provide additional clues toward understanding the physiological regulation and function of H19.

H19, a marker of developmental transition, is reexpressed in human atherosclerotic plaques and is regulated by the insulin family of growth factors in cultured rabbit smooth muscle cells.

PubMed Central

Han, D K; Khaing, Z Z; Pollock, R A; Haudenschild, C C; Liau, G

1996-01-01

H19 is a developmentally regulated gene with putative tumor suppressor activity, and loss of H19 expression may be involved in Wilms' tumorigenesis. In this report, we have performed in situ hybridization analysis of H19 expression during normal rabbit development and in human atherosclerotic plaques. We have also used cultured smooth muscle cells to identify H19 regulatory factors. Our data indicate that H19 expression in the developing skeletal and smooth muscles correlated with specific differentiation events in these tissues. Expression of H19 in the skeletal muscle correlated with nonproliferative, actin-positive muscle cells. In the prenatal blood vessel, H19 expression was both temporally and spatially regulated with initial loss of expression in the inner smooth muscle layers adjacent to the lumen. We also identified H19-positive cells within the adult atherosclerotic lesion and we suggest that these cells may recapitulate earlier developmental events. These results, along with the identification of the insulin family of growth factors as potent regulatory molecules for H19 expression, provide additional clues toward understanding the physiological regulation and function of H19. PMID:8636440

Vorapaxar in atherosclerotic disease management.

PubMed

Cheng, Judy W M; Colucci, Vincent; Howard, Patricia A; Nappi, Jean M; Spinler, Sarah A

2015-05-01

To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases. Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). Two phase III clinical trials with vorapaxar have been published. In patients with non-ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke. Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient's individual bleeding risk. © The Author(s) 2015.

Coronary heart disease risk stratification: pitfalls and possibilities.

PubMed

Negi, Smita; Nambi, Vijay

Atherosclerosis of the coronary arteries, or coronary heart disease (CHD), is the most common cause of mortality in U.S. adults. The pathobiology of atherosclerosis and its complications is a continuum. At one end of the spectrum are young individuals without atherosclerotic disease who have not yet been exposed to lifestyle or other risk factors, and at the other end are patients with manifest atherosclerosis - myocardial infarction, stroke, and disabling peripheral arterial disease - where risk of recurrent disease and death is driven by the same factors initially responsible for the emergence of disease. However, it is clear that while risk factors are important in the development of CHD, not everyone with risk factors develops the disease and not everyone with CHD has risk factors. Furthermore, even similar degrees of exposure to a risk factor leads to disease in some individuals and not in others. Risk prediction, which is crucial in predicting and hence preventing disease, therefore becomes very challenging. In this article we review the currently available risk stratification tools for predicting CHD risk and discuss potential ways to improve risk prediction.

Correlation of inflammation assessed by 18F-FDG PET, active mineral deposition assessed by 18F-fluoride PET, and vascular calcification in atherosclerotic plaque: a dual-tracer PET/CT study.

PubMed

Derlin, Thorsten; Tóth, Zoltán; Papp, László; Wisotzki, Christian; Apostolova, Ivayla; Habermann, Christian R; Mester, Janos; Klutmann, Susanne

2011-07-01

Formation and progression of atherosclerotic plaque is a dynamic and complex process involving various pathophysiologic steps including inflammation and calcification. The purpose of this study was to compare macrophage activity as determined by (18)F-FDG PET and ongoing mineral deposition as measured by (18)F-sodium fluoride PET in atherosclerotic plaque and to correlate these findings with calcified plaque burden as assessed by CT. Forty-five patients were examined by whole-body (18)F-FDG PET, (18)F-sodium fluoride PET, and CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio [TBR]). The pattern of tracer uptake in atherosclerotic lesions was compared after color-coded multistudy image fusion of PET and CT studies. The Fisher exact test and the Spearman correlation coefficient r(s) were used for statistical analysis of image-based results and cardiovascular risk factors. Intra- and interrater reproducibility were evaluated using the Cohen κ. (18)F-sodium fluoride uptake was observed at 105 sites in 27 (60%) of the 45 study patients, and mean TBR was 2.3 ± 0.7. (18)F-FDG uptake was seen at 124 sites in 34 (75.6%) patients, and mean TBR was 1.5 ± 0.3. Calcified atherosclerotic lesions were observed at 503 sites in 34 (75.6%) patients. Eighty-one (77.1%) of the 105 lesions with marked (18)F-sodium fluoride uptake and only 18 (14.5%) of the 124 lesions with (18)F-FDG accumulation were colocalized with arterial calcification. Coincident uptake of both (18)F-sodium fluoride and (18)F-FDG was observed in only 14 (6.5%) of the 215 arterial lesions with radiotracer accumulation. PET/CT with (18)F-FDG and (18)F-sodium fluoride may allow evaluation of distinct pathophysiologic processes in atherosclerotic lesions and might provide information on the complex interactions involved in formation and progression of atherosclerotic plaque.

Diagnosis of vulnerable atherosclerotic plaques by time-resolved fluorescence spectroscopy and ultrasound imaging.

PubMed

Jo, J A; Fang, Q; Papaioannou, T; Qiao, J H; Fishbein, M C; Beseth, B; Dorafshar, A H; Reil, T; Baker, D; Freischlag, J; Shung, K K; Sun, L; Marcu, L

2006-01-01

In this study, time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) and ultrasonography were applied to detect vulnerable (high-risk) atherosclerotic plaque. A total of 813 TR-LIFS measurements were taken from carotid plaques of 65 patients, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified by histopathology as thin, fibrotic, calcified, low-inflamed, inflamed and necrotic lesions. Spectral and time-resolved parameters (normalized intensity values and Laguerre expansion coefficients) were extracted from the TR-LIFS data. Feature selection for classification was performed by either analysis of variance (ANOVA) or principal component analysis (PCA). A stepwise linear discriminant analysis algorithm was developed for detecting inflamed and necrotic lesion, representing the most vulnerable plaques. These vulnerable plaques were detected with high sensitivity (>80%) and specificity (>90%). Ultrasound (US) imaging was obtained in 4 carotid plaques in addition to TR-LIFS examination. Preliminary results indicate that US provides important structural information of the plaques that could be combined with the compositional information obtained by TR-LIFS, to obtain a more accurate diagnosis of vulnerable atherosclerotic plaque.

EphA2 knockdown attenuates atherosclerotic lesion development in ApoE(-/-) mice.

PubMed

Jiang, Hong; Li, Xinyun; Zhang, Xiaoli; Liu, Yan; Huang, Shanying; Wang, Xiaowei

2014-01-01

The inflammatory response of vascular endothelial cells plays important roles in the initiation and progression of atherosclerotic lesions. EphA2 receptor activation promotes the endothelial cell inflammatory response, and its expression is increased in the endothelial cell layer of atherosclerotic plaques. However, the association between EphA2 and atherosclerosis has not been determined. Eight-week-old male ApoE(-/-) mice were systemically infected with adenoassociated virus serotype 9 carrying a small hairpin RNA specifically targeting the EphA2 gene to knock down EphA2 expression in aortic endothelial cells. These mice were then fed a high-cholesterol diet for 12 weeks. Blood was collected for the measurement of plasma lipids. The aortas were harvested to evaluate the atherosclerotic lesion size, macrophage components, and expression of proinflammatory genes using Oil Red O staining, immunofluorescence staining, and molecular biology analysis. The lesions formed in the entire aorta and aortic sinus of the ApoE(-/-) mice with EphA2 knockdown were significantly smaller than those in the control mice (10.7%±3.1% versus 25.1%±4.2%; 0.51±0.02mm(2) versus 0.85±0.03mm(2); n=10; P<.05). Furthermore, the lesions in the ApoE(-/-) mice with EphA2 knockdown displayed reduced inflammation compared with the control mice, as reflected by the decreased macrophage infiltration (8.2%±2.9% versus 22.7%±4%; n=10; P<.05); decreased nuclear factor-κβ activation; and diminished expression of vascular cell adhesion molecule-1, E-selectin, and monocyte chemotactic protein-1 (all P<.05). Our data demonstrate that the EphA2 receptor silencing attenuates the extent and inflammation of atherosclerotic lesions in ApoE(-/-) mice. Thus, EphA2 knockdown in endothelial cells represents a novel therapeutic strategy for patients with atherosclerosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevalence and risk factors associated with peripheral arterial disease in an adult population from Colombia.

PubMed

Urbano, Lorena; Portilla, Eliana; Muñoz, Wilson; Hofman, Albert; Sierra-Torres, Carlos H

Cardiovascular diseases (CVD) are the most important cause of mortality in Latin America, while peripheral arterial disease (PAD) is the third leading cause of atherosclerotic cardiovascular morbidity. To establish the prevalence of PAD and the distribution of traditional CVD risk factors in a population from the Department of Cauca, Colombia. A cross-sectional study was conducted on a total of 10,000 subjects aged ≥40 years, from 36 municipalities. An ankle-brachial index (ABI) ≤ 0.9 in either leg was used as diagnostic criterion of PAD. Overall PAD prevalence was 4.4% (4.7% females vs. 4.0% males), with diabetes being the most prevalent risk factor (23%). Among individuals self-reporting a history of acute myocardial infarction or stroke, PAD prevalence was 31.0% and 8.1%, respectively. After adjusting for potential confounders, PAD was significantly associated with hypertension (OR 4.6; 95% CI; 3.42-6.20), diabetes (4.3; 3.17-5.75), dyslipidaemia (3.1; 2.50-3.88), obesity (1.8; 1.37-2.30), and cigarette smoking (1.6; 1.26-1.94). Analysis for the interaction of risk factors showed that diabetes, dyslipidaemia, and obesity accounted for 13.2 times the risk for PAD (6.9-25.4), and when adding hypertension to the model, the risk effect was the highest (17.2; 8.4-35.1). Hypertension, diabetes, dyslipidaemia, and obesity, but not smoking were strong predictors of PAD. ABI measurement should be routinely performed as a screening test in intermediate and high-risk patients for CVD prevention. This could lead to an early intervention and follow-up on populations at risk, thus, contributing to improve strategies for reducing CVD burden. Copyright © 2017. Publicado por Masson Doyma México S.A.

The Effect of ACE I/D Polymorphisms Alone and With Concomitant Risk Factors on Coronary Artery Disease.

PubMed

Amara, Ahmed; Mrad, Meriem; Sayeh, Aicha; Lahideb, Dhaker; Layouni, Samy; Haggui, Abdeddayem; Fekih-Mrissa, Najiba; Haouala, Habib; Nsiri, Brahim

2018-01-01

Coronary artery disease (CAD), also known as atherosclerotic heart disease, is a leading cause of mortality and morbidity throughout the world. The role of insertion/deletion (I/D) polymorphisms of the angiotensin-converting enzyme (ACE) gene in the etiology of CAD remains to be more completely clarified. The aim of this study was to determine the role of the ACE I/D polymorphism in patients with CAD and to study the association together with traditional risk factors in assessing the risk of CAD. Our study population included 145 Tunisian patients with symptomatic CAD and a control group of 300 people matched for age and sex. All participants in the study were genotyped for the ACE I/D polymorphisms obtained by polymerase chain reaction amplification on genomic DNA. Our analysis showed that the ACE D allele frequency ( P < 10 -3 ; odds ratio [OR] = 5.2; 95% confidence interval [CI] = 3.6-7.6) and DD genotype ( P < 10 -3 ; OR = 6.8; 95% CI = 4.4-10) are significantly more prevalent among patients with CAD than in controls and may be predisposing to CAD. We further found that the risk of CAD is greatly potentiated by several concomitant risk factors (smoking, diabetes, hypertension, dyslipidemia, and a family history of CAD). The ACE D allele may be predictive in individuals who may be at risk of developing CAD. Further investigations of these polymorphisms and their possible synergisms with traditional risk factors for CAD could help to ascertain better predictability for CAD susceptibility.

[Aortic valve calcification prevalence and association with coronary risk factors and atherosclerosis in Mexican population].

PubMed

Acuña-Valerio, Jorge; Rodas-Díaz, Marco A; Macias-Garrido, Enrico; Posadas-Sánchez, Rosalinda; Juárez-Rojas, Juan G; Medina-Urrutia, Aida X; Cardoso-Saldaña, Guillermo C; Joge-Galarza, Esteban; Torres-Tamayo, Margarita; Vargas-Alarcón, Gilberto; Posadas-Romero, Carlos

The prevalence of aortic valve calcification (AVC), strongly influenced by ethnicity, is unknown in Mexican population. The aim of this study was to investigate the prevalence of AVC and its associations with cardiovascular risk factors and coronary artery calcification (CAC), in Mexican subjects. In 1,267 subjects (53% women) without known coronary heart disease, aged 35 to 75 years, AVC and CAC were assessed by multidetector-computed tomography using the Agatston score. Cardiovascular risk factors were documented in all participants. The associations of AVC with CAC and risk factors were assessed by multivariable logistic regression analyses. The overall prevalence of AVC and CAC was 19.89% and 26.5%, respectively. AVC and CAC increased with age and were found more frequently in men (25.5% and 37.1%, respectively) than in women (14.9% and 13.0%, respectively). AVC was observed in only 8.5% of subjects without CAC, while those with CAC 1-99, 100-399, and >400 Agatston units had AVC prevalences of 36.8%, 56.8%, and 84.0%, respectively. The multivariable logistic regression analyses, adjusted for age, gender, obesity, physical inactivity, hypertension, dyslipidemia and high insulin levels, showed that the presence of CAC (OR [CI95%]: 3.23 [2.26-4.60]), obesity (1.94 [1.35-2.79]), male gender (1.44 [1.01-2.05]) and age (1.08 [1.03-1.10]), were significant independent predictors of AVC. Prevalence of AVC is high and significantly associated with atherosclerotic risk factors and CAC in this Mexican population. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Paramagnetic Manganese in the Atherosclerotic Plaque of Carotid Arteries

PubMed Central

Chelyshev, Yury; Ignatyev, Igor; Zanochkin, Alexey; Mamin, Georgy; Sorokin, Boris; Sorokina, Alexandra; Lyapkalo, Natalya; Gizatullina, Nazima; Orlinskii, Sergei

2016-01-01

The search for adequate markers of atherosclerotic plaque (AP) instability in the context of assessment of the ischemic stroke risk in patients with atherosclerosis of the carotid arteries as well as for solid physical and chemical factors that are connected with the AP stability is extremely important. We investigate the inner lining of the carotid artery specimens from the male patients with atherosclerosis (27 patients, 42–64 years old) obtained during carotid endarterectomy by using different analytical tools including ultrasound angiography, X-ray analysis, immunological, histochemical analyses, and high-field (3.4 T) pulse electron paramagnetic resonance (EPR) at 94 GHz. No correlation between the stable and unstable APs in the sense of the calcification is revealed. In all of the investigated samples, the EPR spectra of manganese, namely, Mn2+ ions, are registered. Spectral and relaxation characteristics of Mn2+ ions are close to those obtained for the synthetic (nano) hydroxyapatite species but differ from each other for stable and unstable APs. This demonstrates that AP stability could be specified by the molecular organization of their hydroxyapatite components. The origin of the obtained differences and the possibility of using EPR of Mn2+ as an AP stability marker are discussed. PMID:28078287

Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

PubMed Central

Bossaller, C; Habib, G B; Yamamoto, H; Williams, C; Wells, S; Henry, P D

1987-01-01

The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it. PMID:2432088

Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease.

PubMed

Pasterkamp, Gerard; den Ruijter, Hester M; Libby, Peter

2017-01-01

The concept of the 'vulnerable plaque' originated from pathological observations in patients who died from acute coronary syndrome. This recognition spawned a generation of research that led to greater understanding of how complicated atherosclerotic plaques form and precipitate thrombotic events. In current practice, an increasing number of patients who survive their first event present with non-ST-segment elevation myocardial infarction (NSTEMI) rather than myocardial infarction (MI) with ST-segment elevation (STEMI). The culprit lesions that provide the pathological substrate for NSTEMI can vary considerably from the so-called 'vulnerable plaque'. The shift in clinical presentation of MI and stroke corresponds temporally to a progressive change in the characteristics of human plaques away from the supposed characteristics of vulnerability. These alterations in the structure and function of human atherosclerotic lesions might mirror the modifications that are produced in experimental plaques by lipid lowering, inspired by the vulnerable plaque construct. The shift in the clinical presentations of the acute coronary syndromes mandates a critical reassessment of the underlying mechanisms, proposed risk scores, the results and interpretation of preclinical experiments, as well as recognition of the limitations of the use of population data and samples collected before the application of current preventive interventions.

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice.

PubMed

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-05-01

Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages. Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. © 2015 The British Pharmacological Society.

Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

PubMed Central

Khambata, Rayomand S.; Ghosh, Suborno M.; Rathod, Krishnaraj S.; Thevathasan, Tharssana; Filomena, Federica; Xiao, Qingzhong; Ahluwalia, Amrita

2017-01-01

Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO3−) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitrate-fed mice there is reduced systemic leukocyte rolling and adherence, circulating neutrophil numbers, neutrophil CD11b expression, and myeloperoxidase activity compared with wild-type littermates. Moreover, we show in both the ApoE KO mice and using an acute model of inflammation that this effect upon neutrophils results in consequent reductions in inflammatory monocyte expression that is associated with elevations of the antiinflammatory cytokine interleukin (IL)-10. In summary, we demonstrate that inorganic nitrate suppresses acute and chronic inflammation by targeting neutrophil recruitment and that this effect, at least in part, results in consequent reductions in the inflammatory status of atheromatous plaque, and suggest that this effect may have clinical utility in the prophylaxis of inflammatory atherosclerotic disease. PMID:28057862

Flow in Atherosclerotic Blood Vessels

NASA Astrophysics Data System (ADS)

Berger, Stanley A.; Stroud, Jenn S.

2000-11-01

Atherosclerotic lesions occur in arteries where there are major changes in flow structure, e.g. bifurcations and junctions. The reduction of vessel lumen alters the flow, including the mechanical forces on the walls. We have examined the flow in carotid artery bifurcations with realistic plaque contours. The unsteady, incompressible, Navier-Stokes equations are solved in finite-volume form. Steady and pulsatile flows have been analyzed for laminar and turbulent flows, using for the latter a low-Reynolds number k- ɛ model and a k-ω model. Non-Newtonian viscosity is also considered using a power-law model. In general the very irregular contours of the vessels lead to recirculating regions, strong spatial variations of wall shear stresses, and in some cases, vortex shedding. Even steady inlet flow exhibits fluctuating, unsteady behavior. Neither turbulence models captures all the physics of the flow. The flow, in fact, appears to be transitional and not fully turbulent. For unsteady flow, there are also strong temporal variations of normal and shear stresses, which together with the strong spatial variations, has important implications for the onset and progression of atherosclerotic disease.

Toll-like receptor 7 stimulation by imiquimod induces macrophage autophagy and inflammation in atherosclerotic plaques.

PubMed

De Meyer, Inge; Martinet, Wim; Schrijvers, Dorien M; Timmermans, Jean-Pierre; Bult, Hidde; De Meyer, Guido R Y

2012-05-01

Atherosclerotic plaques tend to rupture as a consequence of a weakened fibrous cap, particularly in the shoulder regions where most macrophages reside. Macrophages express Toll-like receptors to recognize pathogens and eliminate intracellular pathogens by inducing autophagy. Because Toll-like receptor 7 (TLR7) is thought to be expressed in macrophages but not in smooth muscle cells (SMCs), we investigated whether induction of macrophage autophagic death by TLR7 ligand imiquimod can affect the composition of atherosclerotic plaques in favor of their stability. Immunohistochemical staining of human carotid plaques as well as Western blotting of cultured macrophages and SMCs confirmed that TLR7 was expressed in macrophages, but not in SMCs. In vitro experiments showed that only TLR7 expressing cells underwent imiquimod-induced cell death, which was characterized by autophagosome formation. Imiquimod-treated macrophages activated nuclear factor-κB (NF-κB) and released pro-inflammatory cytokines and chemokines. This effect was inhibited by the glucocorticoid dexamethasone. Imiquimod-induced cytokine release was significantly decreased in autophagy-deficient macrophages because these cells died by necrosis at an accelerated pace. Local in vivo administration of imiquimod to established atherosclerotic lesions in rabbit carotid arteries induced macrophage autophagy without induction of cell death, and triggered cytokine production, upregulation of vascular adhesion molecule-1, infiltration of T-lymphocytes, accumulation of macrophages and enlargement of plaque area. Treatment with dexamethasone suppressed these pro-inflammatory effects in vivo. SMCs and endothelial cells in imiquimod-treated plaques were not affected. In conclusion, imiquimod induces macrophage autophagy in atherosclerotic plaques, but stimulates plaque progression through cytokine release and enhanced infiltration of inflammatory cells.

Label-free imaging of atherosclerotic plaques using third-harmonic generation microscopy

PubMed Central

Small, David M.; Jones, Jason S.; Tendler, Irwin I.; Miller, Paul E.; Ghetti, Andre; Nishimura, Nozomi

2017-01-01

Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300 nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human samples. Third harmonic generation (THG) from atherosclerotic plaques revealed morphological details of cellular and extracellular lipid deposits. Simultaneous nonlinear optical signals from the same laser source, including second harmonic generation and endogenous fluorescence, resulted in label-free images of various layers within the diseased vessel wall. The THG signal adds an endogenous contrast mechanism with a practical degree of specificity for atherosclerotic plaques that complements current nonlinear optical methods for the investigation of cardiovascular disease. Our use of whole-mount tissue and backward scattered epi-detection suggests THG could potentially be used in the future as a clinical tool. PMID:29359098

Correlations between gene expression highlight a different activation of ACE/TLR4/PTGS2 signaling in symptomatic and asymptomatic plaques in atherosclerotic patients.

PubMed

Ferronato, Silvia; Scuro, Alberto; Gomez-Lira, Macarena; Mazzucco, Sara; Olivato, Silvia; Turco, Alberto; Elisa, Orlandi; Malerba, Giovanni; Romanelli, Maria Grazia

2018-06-19

Inflammation has a key role and translates the effects of many known risk factors for the disease in atherosclerotic vulnerable plaques. Aiming to look into the elements that induce the development of either a vulnerable or stable atherosclerotic plaque, and considering that inflammation has a central role in the progression of lesions, we analyzed the expression of genes involved in the ACE/TLR4/PTGS2 signaling in carotid plaques of symptomatic and asymptomatic patients. Patients with internal carotid artery stenosis undergoing carotid endarterectomy at Verona University Hospital were included in this study. A total of 71 patients was considered for gene expression analysis (29 atherothrombotic stroke patients and 42 asymptomatic patients). Total RNA was extracted from the excised plaques and expression of PTGS2, ACE, TLR4, PTGER4, PTGER3, EPRAP and ACSL4 genes was analyzed by real-time PCR. The correlation between the pair of genes was studied by Spearman coefficient. From the analyzed genes, we did not observe any individual difference in gene expression but the network of co-expressed genes suggests a different activation of pathways in the two groups of plaques.

Texture based segmentation method to detect atherosclerotic plaque from optical tomography images

NASA Astrophysics Data System (ADS)

Prakash, Ammu; Hewko, Mark; Sowa, Michael; Sherif, Sherif

2013-06-01

Optical coherence tomography (OCT) imaging has been widely employed in assessing cardiovascular disease. Atherosclerosis is one of the major cause cardio vascular diseases. However visual detection of atherosclerotic plaque from OCT images is often limited and further complicated by high frame rates. We developed a texture based segmentation method to automatically detect plaque and non plaque regions from OCT images. To verify our results we compared them to photographs of the vascular tissue with atherosclerotic plaque that we used to generate the OCT images. Our results show a close match with photographs of vascular tissue with atherosclerotic plaque. Our texture based segmentation method for plaque detection could be potentially used in clinical cardiovascular OCT imaging for plaque detection.

Mathematical modeling of atherosclerotic plaque destabilization: Role of neovascularization and intraplaque hemorrhage.

PubMed

Guo, Muyi; Cai, Yan; Yao, Xinke; Li, Zhiyong

2018-08-07

Observational studies have identified angiogenesis from the adventitial vasa vasorum and intraplaque hemorrhage (IPH) as critical factors in atherosclerotic plaque progression and destabilization. Here we propose a mathematical model incorporating intraplaque neovascularization and hemodynamic calculation with plaque destabilization for the quantitative evaluation of the role of neoangiogenesis and IPH in the vulnerable atherosclerotic plaque formation. An angiogenic microvasculature is generated by two-dimensional nine-point discretization of endothelial cell proliferation and migration from the vasa vasorum. Three key cells (endothelial cells, smooth muscle cells and macrophages) and three key chemicals (vascular endothelial growth factors, extracellular matrix and matrix metalloproteinase) are involved in the plaque progression model, and described by the reaction-diffusion partial differential equations. The hemodynamic calculation of the microcirculation on the generated microvessel network is carried out by coupling the intravascular, interstitial and transvascular flow. The plasma concentration in the interstitial domain is defined as the description of IPH area according to the diffusion and convection with the interstitial fluid flow, as well as the extravascular movement across the leaky vessel wall. The simulation results demonstrate a series of pathophysiological phenomena during the vulnerable progression of an atherosclerotic plaque, including the expanding necrotic core, the exacerbated inflammation, the high microvessel density (MVD) region at the shoulder areas, the transvascular flow through the capillary wall and the IPH. The important role of IPH in the plaque destabilization is evidenced by simulations with varied model parameters. It is found that the IPH can significantly speed up the plaque vulnerability by increasing necrotic core and thinning fibrous cap. In addition, the decreased MVD and vessel permeability may slow down the process of

Collagen and related extracellular matrix proteins in atherosclerotic plaque development.

PubMed

Shami, Annelie; Gonçalves, Isabel; Hultgårdh-Nilsson, Anna

2014-10-01

The structure, composition and turnover of the extracellular matrix (ECM) as well as cell-matrix interactions are crucial in the developing atherosclerotic plaque. There is a need for further insight into specific proteins in the ECM and their functions in the developing plaque, and during the last few years a number of publications have highlighted this very important field of research. These novel findings will be addressed in the present review. This review covers literature focused on collagen and ECM proteins interacting with collagen, and what their roles may be in plaque development. Acute myocardial infarction and stroke are common diseases that cause disability and mortality, and the underlying mechanism is often the rupture of a vulnerable atherosclerotic plaque. The vascular ECM and the tissue repair in the atherosclerotic lesion are important players in plaque progression. Understanding how specific proteins in the ECM interact with cells in the plaque and affect the fate of the plaque can lead to new treatments for cardiovascular disease.

Tyrosine phosphorylation of platelet derived growth factor β receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris

PubMed Central

Abe, J; Deguchi, J; Takuwa, Y; Hara, K; Ikari, Y; Tamura, T; Ohno, M; Kurokawa, K

1998-01-01

Background—Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase activation and subsequent cellular migration, proliferation, and vascular contraction.
Aims—To investigate whether the concentration of PDGF β receptor tyrosine phosphorylation obtained from directional coronary atherectomy (DCA) samples correlate with atherosclerotic plaque burden, the ability of diseased vessels to remodel, coronary risk factors, and clinical events.
Methods—DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF β receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF β receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables.
Results—PDGF β receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non-atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control standard, p < 0.0001). As evaluated by stepwise regression analysis, incorporation of both PDGF β receptor tyrosine phosphorylation and immediate gain correlated strongly (adjusted r2 = 0.579) with late loss, although PDGF β receptor tyramine phosphorylation alone correlated poorly with late loss. Multivariate regression analysis of coronary risk factors and clinical events revealed unstable angina as the most significant correlate of PDGF β receptor tyrosine phosphorylation (F value 20.009, p < 0.0001).
Conclusions—PDGF β receptor tyrosine phosphorylation in atherosclerotic lesions is increased compared with non-atherosclerotic arterial tissues. The association of PDGF β receptor tyrosine phosphorylation with

Decreased cathepsin K levels in human atherosclerotic plaques are associated with plaque instability.

PubMed

Zhao, Huiying; Qin, Xiujiao; Wang, Shuai; Sun, Xiwei; Dong, Bin

2017-10-01

Investigating the determinants and dynamics of atherosclerotic plaque instability is a key area of current cardiovascular research. Extracellular matrix degradation from excessive proteolysis induced by enzymes such as cathepsin K (Cat K) is implicated in the pathogenesis of unstable plaques. The current study assessed the expression of Cat K in human unstable atherosclerotic plaques. Specimens of popliteal arteries with atherosclerotic plaques were classified as stable (<40% lipid core plaque area; n=6) or unstable (≥40% lipid core plaque area; n=14) based on histopathological examinations of hematoxylin and eosin stained sections. The expression of Cat K and cystatin C (Cys C) were assessed by immunohistochemical examination and levels of Cat K mRNA were detected by semi-quantitative reverse transcriptase polymerase chain reaction. Morphological changes including a larger lipid core, endothelial proliferation with foam cells and destruction of internal elastic lamina were observed in unstable atherosclerotic plaques. In unstable plaques, the expression of Cat K protein and mRNA was upregulated, whereas Cys C protein expression was downregulated. The interplay between Cat K and Cys C may underlie the progression of plaques from stable to unstable and the current study indicated that Cat K and Cys C are potential targets for preventing and treating vulnerable atherosclerotic plaque ruptures.

Metabolic syndrome is a significant and independent risk factor for increased arterial stiffness in Japanese subjects.

PubMed

Satoh, Hiroki; Kishi, Reiko; Tsutsui, Hiroyuki

2009-12-01

Metabolic syndrome (MetS) has been recognized as a risk factor for cardiovascular disease; however, the impact of MetS on arterial stiffness has not been fully established in the general Japanese population. We analyzed the relationship between MetS and the severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 2744 male and 358 female subjects aged 38-62 years, adjusted for conventional risk factors and C-reactive protein. The prevalence rates of MetS identified by Japanese criteria were 22.7% (n=624) and 7.8% (n=28) in male and female subjects, respectively. The subjects with MetS had significantly greater mean values of baPWV than those without MetS among both male and female subjects (1444+/-209 vs. 1294+/-165 cm/s in male subjects, P<0.001; 1379+/-151 vs. 1220+/-171 cm/s in female subjects, P<0.001). After adjustment for atherosclerotic variables such as age, smoking habits, total cholesterol and C-reactive protein, the odds ratio (OR) of MetS for increased baPWV was 3.65 in male subjects (95% confidence interval (CI): 2.99-4.47, P<0.001) and 8.02 in female subjects (95% CI: 3.18-20.25 P<0.001). In conclusion, MetS was identified as a significant and independent risk factor for increased arterial stiffness in both the male and female general population in Japan.

Deficiency of Endogenous Acute Phase Serum Amyloid A Does Not Impact Atherosclerotic Lesions in ApoE-/- Mice

PubMed Central

De Beer, Maria C; Wroblewski, Joanne M; Noffsinger, Victoria P; Rateri, Debra L; Howatt, Deborah A; Balakrishnan, Anju; Ji, Ailing; Shridas, Preetha; Thompson, Joel C; van der Westhuyzen, Deneys R; Tannock, Lisa R; Daugherty, Alan; Webb, Nancy R; De Beer, Frederick C

2014-01-01

Objective Although elevated plasma concentrations of serum amyloid A (SAA) are strongly associated with increased risk for atherosclerotic cardiovascular disease in humans, the role of SAA in the pathogenesis of lesion formation remains obscure. Our goal was to determine the impact of SAA deficiency on atherosclerosis in hypercholesterolemic mice. Approach and Results ApoE-/- mice, either wild type or deficient in both major acute phase SAA isoforms, SAA1.1 and SAA2.1 (SAAWT and SAAKO, respectively), were fed a normal rodent diet for 50 weeks. Female, but not male SAAKO mice had a modest increase (22%; p ≤ 0.05) in plasma cholesterol concentrations and a 53% increase in adipose mass compared to SAAWT mice that did not impact the plasma cytokine levels or the expression of adipose tissue inflammatory markers. SAA deficiency did not impact lipoprotein cholesterol distributions or plasma triglyceride concentrations in either male or female mice. Atherosclerotic lesion areas measured on the intimal surfaces of the arch, thoracic, and abdominal regions were not significantly different between SAAKO and SAAWT mice in either gender. To accelerate lesion formation, mice were fed a Western diet for 12 weeks. SAA deficiency had no effect on diet-induced alterations in plasma cholesterol, triglyceride or cytokine concentrationsn or on aortic atherosclerotic lesion areas in either male or female mice. In addition, SAA deficiency in male mice had no effect on lesion areas or macrophage accumulation in the aortic roots. Conclusions The absence of endogenous SAA1.1 and 2.1 does not impact atherosclerotic lipid deposition in apoE-/- mice fed either normal or Western diets. PMID:24265416

CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration.

PubMed

Xu, Suining; Li, Lihua; Yan, Jinchuan; Ye, Fei; Shao, Chen; Sun, Zhen; Bao, Zhengyang; Dai, Zhiyin; Zhu, Jie; Jing, Lele; Wang, Zhongqun

2018-01-01

Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration. In vivo study and in vitro study were performed. For the in vivo investigation, CML/CD36 accelerated atherosclerotic progression via promoting the accumulation of macrophage-derived foam cells in aorta and inhibited macrophage-derived foam cells in aorta migrating to the para-aorta lymph node of diabetic apoE -/- mice. For the in vitro investigation, CML/CD36 inhibited RAW264.7-derived foam cell migration through NOX-derived ROS, FAK phosphorylation, Arp2/3 complex activation and F-actin polymerization. Thus, we concluded that CML/CD36 inhibited foam cells of plaque migrating to para-aorta lymph nodes, accelerating atherosclerotic progression. The corresponding mechanism may be via free cholesterol, ROS generation, p-FAK, Arp2/3, F-actin polymerization. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Heart disease - risk factors

MedlinePlus

Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

Lifestyle-related risk factors, smoking status and cardiovascular disease.

PubMed

Giudice, Renata; Izzo, Raffaele; Manzi, Maria Virgina; Pagnano, Giampiero; Santoro, Mario; Rao, Maria Assunta Elena; Di Renzo, Gianfranco; De Luca, Nicola; Trimarco, Valentina

2012-06-01

� 14.1 mg/dL; p < 0.006] and were more often affected by carotid artery atherosclerosis (93.9 % vs 86.1%; p < 0.002) than non-smoking patients. When analysed for dietary and other lifestyle-related risk factors, we found a higher prevalence of carotid atherosclerotic disease in patients consuming less than two meals per day than in those consuming more than two meals per day (96.6% vs 85.7%; p < 0.001), without any significant difference in the mean number of medications taken and in specific classes of medications. Total amount of cigarettes smoked, calculated as packs per year (39.14 ± 16.5 vs 20.81 ± 13.6; p < 0.0001) was higher in patients with a diagnosis of atherosclerotic disease of the carotid artery than in patients free of this disorder, whereas the average age at which people began smoking was lower (17.58 ± 6.3 vs 21.53 ± 10.2 years). In a binary model of logistic regression adjusted for BMI, HDL-C, smoking status and number of daily meals, only smoking status was confirmed to be strongly correlated to clinical evidence of carotid atherosclerosis (p < 0.025). In hypertensive patients, in optimal blood pressure control, smoking status has been shown to be independently associated with an increased maximum arterial IMT (IMTmax). In particular, an increase of the IMT was associated with the total amount of cigarettes smoked (calculated as packs per year) and the average age at which people began smoking.

Protease-Activated Receptor-2 Deficiency Attenuates Atherosclerotic Lesion Progression and Instability in Apolipoprotein E-Deficient Mice

PubMed Central

Zuo, Pengfei; Zuo, Zhi; Zheng, Yueyue; Wang, Xin; Zhou, Qianxing; Chen, Long; Ma, Genshan

2017-01-01

Inflammatory mechanisms are involved in the process of atherosclerotic plaque formation and rupture. Accumulating evidence suggests that protease-activated receptor (PAR)-2 contributes to the pathophysiology of chronic inflammation on the vasculature. To directly examine the role of PAR-2 in atherosclerosis, we generated apolipoprotein E/PAR-2 double-deficient mice. Mice were fed with high-fat diet for 12 weeks starting at ages of 6 weeks. PAR-2 deficiency attenuated atherosclerotic lesion progression with reduced total lesion area, reduced percentage of stenosis and reduced total necrotic core area. PAR-2 deficiency increased fibrous cap thickness and collagen content of plaque. Moreover, PAR-2 deficiency decreased smooth muscle cell content, macrophage accumulation, matrix metallopeptidase-9 expression and neovascularization in plaque. Relative quantitative PCR assay using thoracic aorta revealed that PAR-2 deficiency reduced mRNA expression of inflammatory molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. In vitro experiment, we found that PAR-2 deficiency reduced mRNA expression of interferon-γ, interleukin-6, TNF-α and MCP-1 in macrophage under unstimulated and lipopolysaccharide-stimulated conditions. These results suggest that PAR-2 deficiency attenuates the progression and instability of atherosclerotic plaque. PMID:28959204

Coronary Artery Calcium Scores and Atherosclerotic Cardiovascular Disease Risk Stratification in Smokers: MESA.

PubMed

Leigh, Adam; McEvoy, John W; Garg, Parveen; Carr, J Jeffrey; Sandfort, Veit; Oelsner, Elizabeth C; Budoff, Matthew; Herrington, David; Yeboah, Joseph

2018-02-09

This study assessed the utility of the pooled cohort equation (PCE) and/or coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk assessment in smokers, especially those who were lung cancer screening eligible (LCSE). The U.S. Preventive Services Task Force recommended and the Centers for Medicare & Medicaid Services currently pays for annual screening for lung cancer with low-dose computed tomography scans in a specified group of cigarette smokers. CAC can be obtained from these low-dose scans. The incremental utility of CAC for ASCVD risk stratification remains unclear in this high-risk group. Of 6,814 MESA (Multi-Ethnic Study of Atherosclerosis) participants, 3,356 (49.2% of total cohort) were smokers (2,476 former and 880 current), and 14.3% were LCSE. Kaplan-Meier, Cox proportional hazards, area under the curve, and net reclassification improvement (NRI) analyses were used to assess the association between PCE and/or CAC and incident ASCVD. Incident ASCVD was defined as coronary death, nonfatal myocardial infarction, or fatal or nonfatal stroke. Smokers had a mean age of 62.1 years, 43.5% were female, and all had a mean of 23.0 pack-years of smoking. The LCSE sample had a mean age of 65.3 years, 39.1% were female, and all had a mean of 56.7 pack-years of smoking. After a mean of 11.1 years of follow-up 13.4% of all smokers and 20.8% of LCSE smokers had ASCVD events; 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had an ASCVD event during the follow-up. One SD increase in the PCE 10-year risk was associated with a 68% increase risk for ASCVD events in all smokers (hazard ratio: 1.68; 95% confidence interval: 1.57 to 1.80) and a 22% increase in risk for ASCVD events in the LCSE smokers (hazard ratio: 1.22; 95% confidence interval: 1.00 to 1.47). CAC was associated with increased ASCVD risk in all smokers and in LCSE smokers in all the Cox models. The C-statistic of the PCE for ASCVD was higher in all

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice

PubMed Central

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-01-01

Background and Purpose Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Experimental Approach Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Key Results Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (−31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (−70%) and secretion (−28%) by peritoneal macrophages. Conclusions and Implications Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. PMID:25572138

Dietary Patterns Associated with Lower 10-Year Atherosclerotic Cardiovascular Disease Risk among Urban African-American and White Adults Consuming Western Diets

PubMed Central

Bodt, Barry A.; Stave Shupe, Emily; Zonderman, Alan B.; Evans, Michele K.

2018-01-01

The study’s objective was to determine whether variations in the 2013 American College of Cardiology/American Heart Association 10-year risk for atherosclerotic cardiovascular disease (ASCVD) were associated with differences in food consumption and diet quality. Findings from the baseline wave of Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study 2004–2009, revealed participants consumed a Western diet. Diet quality measures, specifically the Healthy Eating Index (HEI)-2010, Dietary Approaches to Stop Hypertension (DASH) diet and the Mean Adequacy Ratio (MAR), based on two 24-h recalls collected during follow-up HANDLS studies from 2009–2013, were used. Reported foods were assigned to 27 groups. In this cross-sectional analysis, the participants (n = 2140) were categorized into tertiles based on their 10-year ASCVD risk. Lower and upper tertiles were used to determine significantly different consumption rates among the food groups. Ten groups were used in hierarchical case clustering to generate four dietary patterns (DPs) based on group energy contribution. The DP with the highest HEI-2010 score included sandwiches along with vegetables and cheese/yogurt. This DP, along with the pizza/sandwiches DP, had significantly higher DASH and MAR scores and a lower 10-year ASCVD risk, compared to the remaining two DPs–meats/sandwiches and sandwiches/bakery products; thus, Western dietary patterns were associated with different levels of ASCVD 10-year risk. PMID:29385036

[Postprandial lipemia as an atherosclerotic risk factor and fat tolerance test].

PubMed

Ishikawa, T

1999-12-01

Most of our lives are spent in the postprandial state, during which vessel walls are exposed to triglyceride rich lipoproteins-namely, chylomicron and chylomicron remnants. Recent studies showed that coronary artery disease patients even with normal fasting lipid levels had higher concentrations of postprandial lipoproteins than patients without coronary artery disease. Postprandial lipoprotein responses are influenced by various factors such as the postabsorptive concentrations of plasma triglycerides, lipoprotein lipase activity, polymorphisms of apolipoprotein B and apolipoprotein E, dietary fatty acid contents. Oral fat tolerance test is performed to see the postprandial lipoprotein responses. Triglycerides, apolipoprotein B, retinyl-palmitate and remnant like particles in plasma and subfractionated triglyceride rich lipoproteins are measured.

Carotid Artery Disease and Stroke: Assessing Risk with Vessel Wall MRI

PubMed Central

Kerwin, William S.

2012-01-01

Although MRI is widely used to diagnose stenotic carotid arteries, it also detects characteristics of the atherosclerotic plaque itself, including its size, composition, and activity. These features are emerging as additional risk factors for stroke that can be feasibly acquired clinically. This paper summarizes the state of evidence for a clinical role for MRI of carotid atherosclerosis. PMID:23209940

Circulating Wnt inhibitory factor 1 levels are associated with development of cardiovascular disease.

PubMed

Ress, Claudia; Paulweber, Mariya; Goebel, Georg; Willeit, Karin; Rufinatscha, Kerstin; Strobl, Anna; Salzmann, Karin; Kedenko, Ludmilla; Tschoner, Alexander; Staudacher, Gabriele; Iglseder, Bernhard; Tilg, Herbert; Paulweber, Bernhard; Kaser, Susanne

2018-03-29

Wnt signaling is involved in atherosclerotic plaque formation directly and indirectly by modulating cardiovascular risk factors. We investigated whether circulating concentrations of Wnt inhibitors are associated with cardiovascular events in subjects with intermediate cardiovascular risk. 904 non-diabetic subjects participating in the SAPHIR study were assessed. In the SAPHIR study, middle-aged women without overt atherosclerotic disease at study entry were followed up for 10 years. 88 patients of our study cohort developed cardiovascular disease at follow-up (CVD group). Subjects of the CVD group were 1:2 case-control matched for age, sex, BMI and smoking behavior with subjects without overt cardiovascular disease after a 10 year-follow-up (control group). 18 patients of the CVD group and 19 subjects of the control group were retrospectively excluded due to fulfilling exclusion criteria. Baseline circulating sclerostin, dickkopf (DKK)-1, secreted frizzled-related protein (SFRP)-1 and Wnt inhibitory factor (WIF)-1 levels were assessed by ELISA. Baseline systemic SFRP-1 and WIF-1 levels were significantly higher in patients with cardiovascular events (n = 70) when compared to healthy controls (n = 157) while DKK-1 and sclerostin levels were similar in both groups. Logistic regression analysis revealed WIF-1 as a significant predictor of future cardiovascular events. Our data suggest that increased SFRP-1 and WIF-1 levels precede the development of symptomatic atherosclerotic disease. Assessment of systemic WIF-1 levels, which turned out to be independently associated with CVD, might help to early identify patients at intermediate cardiovascular risk. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of Inter-Arm Systolic Blood Pressure Difference with Coronary Atherosclerotic Disease Burden Using Calcium Scoring

PubMed Central

Her, Ae-Young; Cho, Kyoung-Im; Garg, Scot; Kim, Yong Hoon

2017-01-01

Purpose There are no sufficient data on the correlation between inter-arm blood pressure (BP) difference and coronary atherosclerosis found using coronary artery calcium score (CACS). We aimed to investigate if the increased difference in inter-arm BP is independently associated with severity of CACS. Materials and Methods Patients who had ≥3 cardiovascular risk factors or an intermediate Framingham Risk Score (FRS; ≥10) were enrolled. Inter-arm BP difference was defined as the absolute difference in BP in both arms. Quantitative CACS was measured by using coronary computed tomography angiography with the scoring system. Results A total of 261 patients were included in this study. Age (r=0.256, p<0.001), serum creatinine (r=0.139, p=0.030), mean of right arm systolic BP (SBP; r=0.172, p=0.005), mean of left arm SBP (r=0.190, p=0.002), inter-arm SBP difference (r=0.152, p=0.014), and the FRS (r=0.278, p<0.001) showed significant correlation with CACS. The increased inter-arm SBP difference (≥6 mm Hg) was significantly associated with CACS ≥300 [odds ratio (OR) 2.17, 95% confidence interval (CI) 1.12–4.22; p=0.022]. In multivariable analysis, the inter-arm SBP difference ≥6 mm Hg was also significantly associated with CACS ≥300 after adjusting for clinical risk factors (OR 2.34, 95 % CI 1.06–5.19; p=0.036). Conclusion An increased inter-arm SBP difference (≥6 mm Hg) is associated with coronary atherosclerotic disease burden using CACS, and provides additional information for predicting severe coronary calcification, compared to models based on traditional risk factors. PMID:28792138

Association of Inter-Arm Systolic Blood Pressure Difference with Coronary Atherosclerotic Disease Burden Using Calcium Scoring.

PubMed

Her, Ae Young; Cho, Kyoung Im; Garg, Scot; Kim, Yong Hoon; Shin, Eun Seok

2017-09-01

There are no sufficient data on the correlation between inter-arm blood pressure (BP) difference and coronary atherosclerosis found using coronary artery calcium score (CACS). We aimed to investigate if the increased difference in inter-arm BP is independently associated with severity of CACS. Patients who had ≥3 cardiovascular risk factors or an intermediate Framingham Risk Score (FRS; ≥10) were enrolled. Inter-arm BP difference was defined as the absolute difference in BP in both arms. Quantitative CACS was measured by using coronary computed tomography angiography with the scoring system. A total of 261 patients were included in this study. Age (r=0.256, p<0.001), serum creatinine (r=0.139, p=0.030), mean of right arm systolic BP (SBP; r=0.172, p=0.005), mean of left arm SBP (r=0.190, p=0.002), inter-arm SBP difference (r=0.152, p=0.014), and the FRS (r=0.278, p<0.001) showed significant correlation with CACS. The increased inter-arm SBP difference (≥6 mm Hg) was significantly associated with CACS ≥300 [odds ratio (OR) 2.17, 95% confidence interval (CI) 1.12-4.22; p=0.022]. In multivariable analysis, the inter-arm SBP difference ≥6 mm Hg was also significantly associated with CACS ≥300 after adjusting for clinical risk factors (OR 2.34, 95 % CI 1.06-5.19; p=0.036). An increased inter-arm SBP difference (≥6 mm Hg) is associated with coronary atherosclerotic disease burden using CACS, and provides additional information for predicting severe coronary calcification, compared to models based on traditional risk factors. © Copyright: Yonsei University College of Medicine 2017

Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: Synopsis of the 2013 ACC/AHA cholesterol guideline

USDA-ARS?s Scientific Manuscript database

Atherosclerotic cardiovascular disease (ASCVD) is the leading U.S. cause of death, lost quality of life and medical costs. Nearly one in three Americans die from heart disease and stroke. Most ASCVD is preventable through a healthy lifestyle and effective treatment of cholesterol and blood pressure...

Diminazene enhances stability of atherosclerotic plaques in ApoE-deficient mice

PubMed Central

Fraga-Silva, Rodrigo A.; Montecucco, Fabrizio; Costa-Fraga, Fabiana P.; Nencioni, Alessio; Caffa, Irene; Bragina, Maiia E.; Mach, François; Raizada, Mohan K.; Santos, Robson A.S.; da Silva, Rafaela F.; Stergiopulos, Nikolaos

2017-01-01

Angiotensin (Ang) II contributes to the development of atherosclerosis, while Ang-(1–7) has atheroprotective actions. Accordingly, angiotensin-converting enzyme 2 (ACE2), which breaks-down Ang II and forms Ang-(1–7), has been suggested as a target against atherosclerosis. Here we investigated the actions of diminazene, a recently developed ACE2 activator compound, in a model of vulnerable atherosclerotic plaque. Atherosclerotic plaque formation was induced in the carotid artery of ApoE-deficient mice by a shear stress (SS) modiffer device. The animals were treated with diminazene (15 mg/kg/day) or vehicle. ACE2 was strongly expressed in the aortic root and low SS-induced carotid plaques, but poorly expressed in the oscillatory SS-induced carotid plaques. Diminazene treatment did not change the lesion size, but ameliorated the composition of aortic root and low SS-induced carotid plaques by increasing collagen content and decreasing both MMP-9 expression and macrophage infiltration. Interestingly, these beneficial effects were not observed in the oscillatory SS-induced plaque. Additionally, diminazene treatment decreased intraplaque ICAM-1 and VCAM-1 expression, circulating cytokine and chemokine levels and serum triglycerides. In summary, ACE2 was distinctively expressed in atherosclerotic plaques, which depends on the local pattern of shear stress. Moreover, diminazene treatment enhances the stability of atherosclerotic plaques. PMID:26304699

A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation.

PubMed

Massberg, Steffen; Brand, Korbinian; Grüner, Sabine; Page, Sharon; Müller, Elke; Müller, Iris; Bergmeier, Wolfgang; Richter, Thomas; Lorenz, Michael; Konrad, Ildiko; Nieswandt, Bernhard; Gawaz, Meinrad

2002-10-07

The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE(-)(/)(-) mice before the development of manifest atherosclerotic lesions. Platelet-endothelial cell interaction involved both platelet glycoprotein (GP)Ibalpha and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE(-)(/)(-) mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process.

Integrating Soluble Biomarkers and Imaging Technologies in the Identification of Vulnerable Atherosclerotic Patients

PubMed Central

Páramo, José A.; Rodríguez JA, José A.; Orbe, Josune

2006-01-01

The clinical utility of a biomarker depends on its ability to identify high-risk individuals to optimally manage the patient. A new biomarker would be of clinical value if it is accurate and reliable, provides good sensitivity and specificity, and is available for widespread application. Data are accumulating on the potential clinical utility of integrating imaging technologies and circulating biomarkers for the identification of vulnerable (high-risk) cardiovascular patients. A multi-biomarker strategy consisting of markers of inflammation, hemostasis and thrombosis, proteolysis and oxidative stress, combined with new imaging modalities (optical coherence tomography, virtual histology plus IVUS, PET) can increase our ability to identify such thombosis-prone patients. In an ideal scenario, cardiovascular biomarkers and imaging combined will provide a better diagnostic tool to identify high-risk individuals and also more efficient methods for effective therapies to reduce such cardiovascular risk. However, additional studies are required in order to show that this approach can contribute to improved diagnostic and therapeutic of atherosclerotic disease. PMID:19690647

Integrating soluble biomarkers and imaging technologies in the identification of vulnerable atherosclerotic patients.

PubMed

Páramo, José A; Rodríguez Ja, José A; Orbe, Josune

2007-02-07

The clinical utility of a biomarker depends on its ability to identify high-risk individuals to optimally manage the patient. A new biomarker would be of clinical value if it is accurate and reliable, provides good sensitivity and specificity, and is available for widespread application. Data are accumulating on the potential clinical utility of integrating imaging technologies and circulating biomarkers for the identification of vulnerable (high-risk) cardiovascular patients. A multi-biomarker strategy consisting of markers of inflammation, hemostasis and thrombosis, proteolysis and oxidative stress, combined with new imaging modalities (optical coherence tomography, virtual histology plus IVUS, PET) can increase our ability to identify such thombosis-prone patients. In an ideal scenario, cardiovascular biomarkers and imaging combined will provide a better diagnostic tool to identify high-risk individuals and also more efficient methods for effective therapies to reduce such cardiovascular risk. However, additional studies are required in order to show that this approach can contribute to improved diagnostic and therapeutic of atherosclerotic disease.

Characterization of atherosclerotic plaques by cross-polarization optical coherence tomography

NASA Astrophysics Data System (ADS)

Gubarkova, Ekaterina V.; Dudenkova, Varvara V.; Feldchtein, Felix I.; Timofeeva, Lidia B.; Kiseleva, Elena B.; Kuznetsov, Sergei S.; Moiseev, Alexander A.; Gelikonov, Gregory V.; Vitkin, Alex I.; Gladkova, Natalia D.

2016-02-01

We combined cross-polarization optical coherence tomography (CP OCT) and non-linear microscopy based on second harmonic generation (SHG) and two-photon-excited fluorescence (2PEF) to assess collagen and elastin fibers in the development of the atherosclerotic plaque (AP). The study shows potential of CP OCT for the assessment of collagen and elastin fibers condition in atherosclerotic arteries. Specifically, the additional information afforded by CP OCT, related to birefringence and cross-scattering properties of arterial tissues, may improve the robustness and accuracy of assessment about the microstructure and composition of the plaque for different stages of atherosclerosis.

Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis

NASA Astrophysics Data System (ADS)

Tearney, Guillermo J.; Bouma, Brett E.

2002-04-01

Improved methods are needed to identify the vulnerable coronary plaques responsible for acute myocardial infraction or sudden cardiac death. We describe a method for characterizing the structure and biomechanical properties of atherosclerotic plaques based on speckle pattern fluctuations. Near-field speckle images were acquired from five human aortic specimens ex vivo. The speckle decorrelation time constant varied significantly for vulnerable aortic plaques (τ = 40 ms) versus stable plaques (τ = 400 ms) and normal aorta (τ = 500 ms). These initial results indicate that different atherosclerotic plaque types may be distinguished by analysis of temporal and spatial speckle pattern fluctuations.

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, Dong Ju; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA; Kim, Soo Yeon

2012-10-19

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murinemore » model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.« less

American College of Cardiology/American Heart Association (ACC/AHA) Class I Guidelines for the Treatment of Cholesterol to Reduce Atherosclerotic Cardiovascular Risk: Implications for US Hispanics/Latinos Based on Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

PubMed

Qureshi, Waqas T; Kaplan, Robert C; Swett, Katrina; Burke, Gregory; Daviglus, Martha; Jung, Molly; Talavera, Gregory A; Chirinos, Diana A; Reina, Samantha A; Davis, Sonia; Rodriguez, Carlos J

2017-05-11

The prevalence estimates of statin eligibility among Hispanic/Latinos living in the United States under the new 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines are not known. We estimated prevalence of statin eligibility under 2013 ACC/AHA and 3rd National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP III) guidelines among Hispanic Community Health Study/Study of Latinos (n=16 415; mean age 41 years, 40% males) by using sampling weights calibrated to the 2010 US census. We examined the characteristics of Hispanic/Latinos treated and not treated with statins under both guidelines. We also redetermined the statin-therapy eligibility by using black risk estimates for Dominicans, Cubans, Puerto Ricans, and Central Americans. Compared with NCEP/ATP III guidelines, statin eligibility increased from 15.9% (95% CI 15.0-16.7%) to 26.9% (95% CI 25.7-28.0%) under the 2013 ACC/AHA guidelines. This was mainly driven by the ≥7.5% atherosclerotic cardiovascular disease risk criteria (prevalence 13.9% [95% CI 13.0-14.7%]). Of the participants eligible for statin eligibility under NCEP/ATP III and ACC/AHA guidelines, only 28.2% (95% CI 26.3-30.0%) and 20.6% (95% CI 19.4-21.9%) were taking statins, respectively. Statin-eligible participants who were not taking statins had a higher prevalence of cardiovascular risk factors compared with statin-eligible participants who were taking statins. There was no significant increase in statin eligibility when atherosclerotic cardiovascular disease risk was calculated by using black estimates instead of recommended white estimates (increase by 1.4%, P =0.12) for Hispanic/Latinos. The eligibility of statin therapy increased consistently across all Hispanic/Latinos subgroups under the 2013 ACC/AHA guidelines and therefore will potentially increase the number of undertreated Hispanic/Latinos in the United States. © 2017 The Authors. Published on behalf of the American

Evaluation of 99mTc labeled diadenosine tetraphosphate as an atherosclerotic plaque imaging agent in experimental models.

PubMed

Cao, Wei; Zhang, Yongxue; An, Rui

2006-01-01

The potential of 99mTc labeled P1, P4-di (adenosine-5')-tetraphosphate (Ap4A) for imaging experimental atherosclerotic plaques was evaluated in New Zealand white (NZW) rabbits. To label the 99mTc to Ap4A, stannous tartrate solution was used. 99mTc-Ap4A was purified on a Sephadex G-25 column. The radiochemistry purities of 99mTc-Ap4A were 85% to 91%. Biodistribution study revealed 99mTc-Ap4A cleared from blood rapidly. Thirty min after 99mTc-Ap4A administrated on NZW atherosclerotic rabbits, lesion to blood (target/blood, T/B) ratio was 3.17 +/- 1.27, and lesions to normal (target/non-target, T/NT) ratio was 5.23 +/- 1.87. Shadows of atherosclerotic plaques were clearly visible on radioautographic film. Aortas with atherosclerotic plaques also could be seen on ex vivo gamma camera images. Atherosclerotic abdominal aortas were clearly visible on in vivo images 15 min to 3 h after 99mTc-Ap4A administration. 99mTc-labeled Ap4A can be used for rapid noninvasive detection of experimental atherosclerotic plaque.

Near-infrared hyperspectral imaging of atherosclerotic tissue phantom

NASA Astrophysics Data System (ADS)

Ishii, K.; Nagao, R.; Kitayabu, A.; Awazu, K.

2013-06-01

A method to identify vulnerable plaques that are likely to cause acute coronary events has been required. The object of this study is identifying vulnerable plaques by hyperspectral imaging in near-infrared range (NIR-HSI) for an angioscopic application. In this study, NIR-HSI of atherosclerotic tissue phantoms was demonstrated under simulated angioscopic conditions. NIR-HSI system was constructed by a NIR super continuum light and a mercury-cadmium-telluride camera. Spectral absorbance values were obtained in the wavelength range from 1150 to 2400 nm at 10 nm intervals. The hyperspectral images were constructed with spectral angle mapper algorithm. As a result, detections of the lipid area in the atherosclerotic tissue phantom under angioscopic observation conditions were achieved especially in the wavelength around 1200 nm, which corresponds to the second overtone of CH stretching vibration mode.

A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation

PubMed Central

Massberg, Steffen; Brand, Korbinian; Grüner, Sabine; Page, Sharon; Müller, Elke; Müller, Iris; Bergmeier, Wolfgang; Richter, Thomas; Lorenz, Michael; Konrad, Ildiko; Nieswandt, Bernhard; Gawaz, Meinrad

2002-01-01

The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE − / − mice before the development of manifest atherosclerotic lesions. Platelet–endothelial cell interaction involved both platelet glycoprotein (GP)Ibα and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE − / − mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process. PMID:12370251

Acidemia and blood free fatty acids: analysis of cardiovascular risk factors in a new context.

PubMed

Reis, António Heitor

2017-03-01

Following a hypothesis developed in an earlier paper, here it is discussed how deviations of blood pH from the normal range (namely states of acidemia) together with high blood levels of free fatty acids (FFA) may offer a rationale for many important risk factors for cardiovascular diseases (CVD) by shaping a context for formation of fatty acid micelles and vesicles with an acidic core, which fuse with the endothelia, disrupt vital cell processes, and thereby may initiate atherosclerotic plaque formation. Acidemia may arise primarily from dysregulation of the systemic buffers that control blood pH, chronic diseases of kidneys and lungs, inappropriate diet, or may be induced by some common drugs. The level of free fatty acids may be increased and maintained high by chronic stress, and adrenergic shocks. Elevated concentrations of blood FFA in a context of acidemia allow to understand important cardiovascular aspects: the increased risk of menopausal women, the protective effects of physical exercise, the changes in vascular behavior characteristic of metabolic acidosis/acidemia, the role of diet in the pH balance, on how some known medicines like metformin, steroids, NSAIDS, proton pump inhibitors, and calcium supplements may influence CVD risk, and an explanation is offered for the role of statins.

Endoplasmic reticulum stress in perivascular adipose tissue promotes destabilization of atherosclerotic plaque by regulating GM-CSF paracrine.

PubMed

Ying, Ru; Li, Sheng-Wei; Chen, Jia-Yuan; Zhang, Hai-Feng; Yang, Ying; Gu, Zhen-Jie; Chen, Yang-Xin; Wang, Jing-Feng

2018-04-18

Perivascular adipose tissue (PVAT) accelerates plaque progression and increases cardiovascular risk. We tested the hypothesis that PVAT contributed to plaque vulnerability and investigated whether endoplasmic reticulum stress (ER stress) in PVAT played an important role in vulnerable plaque. We transplanted thoracic aortic PVAT or subcutaneous adipose tissue as a control, from donor mice to carotid arteries of recipient apolipoprotein E deficient (apoE -/- ) mice after removing carotid artery collar placed for 6 weeks. Two weeks after transplantation, ER stress inhibitor 4-phenyl butyric acid (4-PBA) was locally administrated to the transplanted PVAT and then animals were euthanized after 4 weeks. Immunohistochemistry was performed to quantify plaque composition and neovascularization. Mouse angiogenesis antibody array kit was used to test the angiogenic factors produced by transplanted adipose tissue. In vitro tube formation assay, scratch wound migration assay and mouse aortic ring assay were used to assess the angiogenic capacity of supernatant of transplanted PVAT. Ultrastructural detection by transmission electron microscopy showed transplanted PVAT was a mixed population of white and brown adipocytes with abundant mitochondria. Transplanted PVAT increased the intraplaque macrophage infiltration, lipid core, intimal and vasa vasorum neovascularization and MMP2/9 expression in plaque while decreased smooth muscle cells and collagen in atherosclerotic plaque, which were restored by local 4-PBA-treatment. Antibody array analysis showed that 4-PBA reduced several angiogenic factors [Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), MCP-1, IL-6] secreted by PVAT. Besides, conditioned medium from 4-PBA treated-PVAT inhibited tube formation and migration capacity of endothelial cells and ex vivo mouse aortic ring angiogenesis compared to conditioned medium from transplanted PVAT. mRNA expression and protein levels of GM-CSF were markedly elevated in

Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.

PubMed

Ulrich, Victoria; Rotllan, Noemi; Araldi, Elisa; Luciano, Amelia; Skroblin, Philipp; Abonnenc, Mélanie; Perrotta, Paola; Yin, Xiaoke; Bauer, Ashley; Leslie, Kristen L; Zhang, Pei; Aryal, Binod; Montgomery, Rusty L; Thum, Thomas; Martin, Kathleen; Suarez, Yajaira; Mayr, Manuel; Fernandez-Hernando, Carlos; Sessa, William C

2016-06-01

Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement of plaque extracellular matrix (ECM) may improve plaque morphology and stabilize lesions. Here, we demonstrate that chronic administration of LNA-miR-29 into an atherosclerotic mouse model improves indices of plaque morphology. This occurs due to upregulation of miR-29 target genes of the ECM (col1A and col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, and reduced necrotic zones. Sustained LNA-miR-29 treatment did not affect circulating lipids, blood chemistry, or ECM of solid organs including liver, lung, kidney, spleen, or heart. Collectively, these data support the idea that antagonizing miR-29 may promote beneficial plaque remodeling as an independent approach to stabilize vulnerable atherosclerotic lesions. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Endotoxin, Toll-like Receptor-4, and Atherosclerotic Heart Disease

PubMed Central

Horseman, Michael A.; Surani, Salim; Bowman, John D.

2017-01-01

Background: Endotoxin is a lipopolysaccharide (LPS) constituent of the outer membrane of most gram negative bacteria. Ubiquitous in the environment, it has been implicated as a cause or con-tributing factor in several disparate disorders from sepsis to heatstroke and Type II diabetes mellitus. Starting at birth, the innate immune system develops cellular defense mechanisms against environmen-tal microbes that are in part modulated through a series of receptors known as toll-like receptors. Endo-toxin, often referred to as LPS, binds to toll-like receptor 4 (TLR4)/ myeloid differentiation protein 2 (MD2) complexes on various tissues including cells of the innate immune system, smooth muscle and endothelial cells of blood vessels including coronary arteries, and adipose tissue. Entry of LPS into the systemic circulation ultimately leads to intracellular transcription of several inflammatory mediators. The subsequent inflammation has been implicated in the development and progression atherosclerosis and subsequent coronary artery disease and heart failure. Objective: The potential roles of endotoxin and TLR4 are reviewed regarding their role in the pathogen-esis of atherosclerotic heart disease. Conclusion: Atherosclerosis is initiated by inflammation in arterial endothelial and subendothelial cells, and inflammatory processes are implicated in its progression to clinical heart disease. Endotoxin and TLR4 play a central role in the inflammatory process, and represent potential targets for therapeutic intervention. Therapy with HMG-CoA inhibitors may reduce the expression of TLR4 on monocytes. Other therapeutic interventions targeting TLR4 expression or function may prove beneficial in athero-sclerotic disease prevention and treatment.

The Interleukin-6 Gene Promoter Polymorphism -174 and Atherosclerotic Events in Overweight Transplanted Patients

PubMed Central

Bamoulid, Jamal; Courivaud, Cécile; Deschamps, Marina; Gaugler, Béatrice; Tiberghien, Pierre; Chalopin, Jean-Marc; Saas, Philippe; Ducloux, Didier

2011-01-01

Chronic inflammation plays a pivotal role in atherosclerosis. We hypothesized that combining overweight and a greater genetic capacity to produce IL-6 predicted by IL-6 gene promoter polymorphism at position -174 (G→C) may allow to identify individuals exhibiting higher IL-6 and C-reactive protein (CRP) concentrations with a higher risk of atherosclerotic events (AE). The occurrence of AE was analyzed with respect to body mass index, IL-6 gene promoter polymorphism at position -174 (G→C), and other relevant risk factors, retrospectively, in 217 renal transplant recipients and, prospectively, in 132. Circulating IL-6 concentrations were closely related to BMI (r = 0.55, P = .0005). In overweight patients, serum IL-6 concentration was found to be significantly lower in C carriers than in GG patients (4.2 [1.0–5.1] versus 7.3 pg/mL [4.4–100]; P = .025). The incidence of AE was higher in overweight GG patients (29.5% versus 10.1%; P = .0003). In multivariate analysis, overweight-GG had an increased risk to develop AE (HR 2.96 [95% CI 1.09–8.04], P = .034 in the retrospective cohort, and HR 2.99 [95% CI 0.92–9.33], P = .069 in the prospective cohort). All these data are consistent with a role for both genetic and environmental determinants of inflammation (white adipose tissue mass) in the development of AE in renal transplanted patients. PMID:21766010

Risk Factors for Scleroderma

MedlinePlus

... You are here: Home For Patients Risk Factors Risk Factors for Scleroderma The cause of scleroderma is ... what biological factors contribute to scleroderma pathogenesis. Genetic Risk Scleroderma does not tend to run in families ...

Grape seed procyanidins improve atherosclerotic risk index and induce liver CYP7A1 and SHP expression in healthy rats.

PubMed

Del Bas, Josep Maria; Fernández-Larrea, Juan; Blay, Mayte; Ardèvol, Anna; Salvadó, Maria Josepa; Arola, Lluis; Bladé, Cinta

2005-03-01

Moderate consumption of red wine reduces risk of death from cardiovascular disease. The polyphenols in red wine are ultimately responsible for this effect, exerting antiatherogenic actions through their antioxidant capacities and modulating intracellular signaling pathways and transcriptional activities. Lipoprotein metabolism is crucial in atherogenesis, and liver is the principal organ controlling lipoprotein homeostasis. This study was intended to identify the primary effects of procyanidins, the most abundant polyphenols in red wine, on both plasma lipoprotein profile and the expression of genes controlling lipoprotein homeostasis in the liver. We show that procyanidins lowered plasma triglyceride, free fatty acids, apolipoprotein B (apoB), LDL-cholesterol and nonHDL:nonLDL-cholesterol levels and slightly increased HDL-cholesterol. Liver mRNA levels of small heterodimer partner (SHP), cholesterol 7alpha-hydroxylase (CYP7A1), and cholesterol biosynthetic enzymes increased, whereas those of apoAII, apoCI, and apoCIII decreased. Lipoprotein lipase (LPL) mRNA levels increased in muscle and decreased in adipose tissue. In conclusion, procyanidins improve the atherosclerotic risk index in the postprandial state, inducing in the liver the overexpression of CYP7A1 (suggesting an increase of cholesterol elimination via bile acids) and SHP, a nuclear receptor emerging as a key regulator of lipid homeostasis at the transcriptional level. These results could explain, at least in part, the beneficial long-term effects associated with moderate red wine consumption.

Anti-atherosclerotic and anti-inflammatory actions of sesame oil.

PubMed

Narasimhulu, Chandrakala Aluganti; Selvarajan, Krithika; Litvinov, Dmitry; Parthasarathy, Sampath

2015-01-01

Atherosclerosis, a major form of cardiovascular disease, has now been recognized as a chronic inflammatory disease. Nonpharmacological means of treating chronic diseases have gained attention recently. We previously reported that sesame oil has anti-atherosclerotic properties. In this study, we have determined the mechanisms by which sesame oil might modulate atherosclerosis by identifying genes and inflammatory markers. Low-density lipoprotein receptor knockout (LDLR(-/-)) female mice were fed with either an atherogenic diet or an atherogenic diet reformulated with sesame oil (sesame oil diet). Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Plasma samples were used for cytokine analysis. RNA was extracted from the liver tissue and used for global gene arrays. The sesame oil diet significantly reduced atherosclerotic lesions, plasma cholesterol, triglyceride, and LDL cholesterol levels in LDLR(-/-) mice. Plasma inflammatory cytokines, such as MCP-1, RANTES, IL-1α, IL-6, and CXCL-16, were significantly reduced, demonstrating an anti-inflammatory property of sesame oil. Gene array analysis showed that sesame oil induced many genes, including ABCA1, ABCA2, APOE, LCAT, and CYP7A1, which are involved in cholesterol metabolism and reverse cholesterol transport. In conclusion, our studies suggest that a sesame oil-enriched diet could be an effective nonpharmacological treatment for atherosclerosis by controlling inflammation and regulating lipid metabolism.

The 2013 ACC/AHA 10-year atherosclerotic cardiovascular disease risk index is better than SCORE and QRisk II in rheumatoid arthritis: is it enough?

PubMed

Ozen, Gulsen; Sunbul, Murat; Atagunduz, Pamir; Direskeneli, Haner; Tigen, Kursat; Inanc, Nevsun

2016-03-01

To determine the ability of the new American College of Cardiology and American Heart Association (ACC/AHA) 10-year atherosclerotic cardiovascular disease (ASCVD) risk algorithm in detecting high cardiovascular (CV) risk, RA patients identified by carotid ultrasonography (US) were compared with Systematic Coronary Risk Evaluation (SCORE) and QRisk II algorithms. SCORE, QRisk II, 2013 ACC/AHA 10-year ASCVD risk and EULAR recommended modified versions were calculated in 216 RA patients. In sonographic evaluation, carotid intima-media thickness >0.90 mm and/or carotid plaques were used as the gold standard test for subclinical atherosclerosis and high CV risk (US+). Eleven (5.1%), 15 (6.9%) and 44 (20.4%) patients were defined as having high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. Fifty-two (24.1%) patients were US + and of those, 8 (15.4%), 7 (13.5%) and 23 (44.2%) patients were classified as high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. The ACC/AHA 10-year ASCVD risk index better identified US + patients than SCORE and QRisk II (P < 0.0001). With EULAR modification, reclassification from moderate to high risk occurred only in two, five and seven patients according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. The 2013 ACC/AHA 10-year ASCVD risk estimator was better than the SCORE and QRisk II indices in RA, but still failed to identify 55% of high risk patients. Furthermore adjustment of threshold and EULAR modification did not work well. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Intra- and extracranial atherosclerotic disease in acute spontaneous intracerebral hemorrhage.

PubMed

Sato, Shoichiro; Uehara, Toshiyuki; Hayakawa, Mikito; Nagatsuka, Kazuyuki; Minematsu, Kazuo; Toyoda, Kazunori

2013-09-15

There is little information about intracranial atherosclerotic disease (ICAD) and extracranial atherosclerotic disease (ECAD) in patients with acute spontaneous intracerebral hemorrhage (ICH). The purpose of the present study was to elucidate the prevalence of and the factors that correlate with ICAD and ECAD in patients with ICH. A total of 274 patients with acute spontaneous ICH were enrolled. ICAD and ECAD (moderate to severe stenosis or occlusion) were mainly assessed by intracranial magnetic resonance angiography and carotid duplex sonography, respectively. Fifty-one patients (19%) had ICAD or ECAD; 32 had ICAD, and 21 had ECAD. On multivariable analyses, age (OR, 1.52; 95% CI, 1.06-2.28 for every 10 years), monocyte count (OR, 1.37; 95% CI, 1.02-1.87 for every 100/mm(3)), hemoglobin A1c (OR, 2.25; 95% CI, 1.08-5.15 for every 1%), and low-density lipoprotein cholesterol levels (OR, 1.23; 95% CI, 1.08-1.42 for every 10mg/dL) were independently associated with ICAD. Age (OR, 2.20; 95% CI, 1.20-4.38 for 10 years) and dyslipidemia (OR, 3.95; 95% CI, 1.01-15.97) were independently associated with ECAD. ICAD and ECAD were detected in approximately one-fifth of patients with spontaneous ICH. Age and dyslipidemia (or lipid profile) were associated with both ICAD and ECAD. Monocyte count and hemoglobin A1c were associated with ICAD. © 2013. Published by Elsevier B.V. All rights reserved.

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

PubMed

Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang; Jiang, Zhi-xin; Chen, Xiao-min

2015-01-01

Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties

PubMed Central

Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang

2015-01-01

Background and objectives Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Subjects and methods Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Results Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with

Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging.

PubMed

Tarkin, Jason M; Joshi, Francis R; Evans, Nicholas R; Chowdhury, Mohammed M; Figg, Nichola L; Shah, Aarti V; Starks, Lakshi T; Martin-Garrido, Abel; Manavaki, Roido; Yu, Emma; Kuc, Rhoda E; Grassi, Luigi; Kreuzhuber, Roman; Kostadima, Myrto A; Frontini, Mattia; Kirkpatrick, Peter J; Coughlin, Patrick A; Gopalan, Deepa; Fryer, Tim D; Buscombe, John R; Groves, Ashley M; Ouwehand, Willem H; Bennett, Martin R; Warburton, Elizabeth A; Davenport, Anthony P; Rudd, James H F

2017-04-11

Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([ 18 F]FDG PET), [ 18 F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. This study tested the efficacy of gallium-68-labeled DOTATATE ( 68 Ga-DOTATATE), a somatostatin receptor subtype-2 (SST 2 )-binding PET tracer, for imaging atherosclerotic inflammation. We confirmed 68 Ga-DOTATATE binding in macrophages and excised carotid plaques. 68 Ga-DOTATATE PET imaging was compared to [ 18 F]FDG PET imaging in 42 patients with atherosclerosis. Target SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68 Ga-DOTATATE ligand binding to SST 2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68 Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68 Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBR max ) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68 Ga-DOTATATE mTBR max predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [ 18 F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [ 18 F]FDG mTBR max differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [ 18 F]FDG spillover rendered coronary

Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development.

PubMed

Hamlyn, Jess; Duhig, Michael; McGrath, John; Scott, James

2013-05-01

Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors. Copyright © 2012 Elsevier Inc

An ultrasound-based comparative study on carotid plaques in HIV-positive patients vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory lesions?

PubMed

Maggi, Paolo; Perilli, Francesco; Lillo, Antonio; Carito, Valentina; Epifani, Giuseppe; Bellacosa, Chiara; Pastore, Giuseppe; Regina, Guido

2007-02-01

We have previously described two cases of HIV-1-positive patients undergoing surgery for stenosis of the internal carotid arteries. Histology revealed an extensive inflammatory infiltration of the vascular wall and no evidence of atheromasic plaque. This unexpected pattern of carotid damage prompted us to perform a more accurate investigation of the characteristics of carotid plaques in a group of HIV-positive patients. The results were compared with those obtained from young patients affected by atherosclerosis of the epi-aortic vessels and patients with arteritis. The patients underwent ultrasonography of the epi-aortic vessels using one of the latest generation power color-Doppler with 7.5 MHz probes. The study population included 61 HIV-positive patients and 47 HIV-negative patients (37 atherosclerotic and 10 with arteritis). Compared with HIV-negative atherosclerotic patients, there were significantly higher proportions of HIV-positive patients with iso-hypoechogenic lesions (81.8 vs. 29%) that were homogeneous both in their parietal and endoluminal portions (96.7 vs. 21.6% and 88.5 vs. 54.0%, respectively), with a smooth or slightly irregular surface (99.0 vs. 56.7%) (P=0.001 for all differences). No statistically significant differences were seen between HIV-positive and arteritis patients. Our study evidenced that the ultrasonographic structure of the epi-aortic lesions in HIV-positive patients substantially differ from those of the plaques in atherosclerotic patients, although they share similar characteristics with patients affected by arteritis. Further investigations are warranted to better define the structure and the mechanism of onset of these lesions.

A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

NASA Astrophysics Data System (ADS)

Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

2014-01-01

Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

Deep subcortical infarct burden in relation to apolipoprotein B/AI ratio in patients with intracranial atherosclerotic stenosis.

PubMed

Park, J-H; Hong, K-S; Lee, J; Kim, Y-J; Song, P

2013-04-01

Pre-existing brain infarct (PBI), frequently seen on magnetic resonance imaging and usually silent, is recognized as a risk factor for future stroke. Increased apolipoprotein B (apoB)/apoAI ratio is known to be a risk predictor of ischaemic stroke and is associated with intracranial atherosclerotic stenosis (ICAS). However, little is known about the association of apoB/apoAI ratio with PBI. A total of 522 statin-/fibrate-naïve Korean patients, who experienced acute ischaemic stroke, were categorized into three groups: ICAS (n=254), extracranial (n=51), and no cerebral atherosclerotic stenosis (n=217). We explored the association between apoB/apoAI ratio and PBI lesions according to atherosclerosis type (ICAS, ECAS, and NCAS), PBI location (deep subcortical [ds-PBI] versus hemispheric [h-PBI]), and symptomatic PBI (s-PBI) which was relevant to a prior clinical stroke event. Pre-existing brain infarct(+) patients showed a higher apoB/apoAI ratio than PBI(-) patients (0.81 ± 0.28 vs. 0.72 ± 0.23, P<0.001). In ICAS group, patients with higher apoB/apoAI ratio quartiles had more PBIs, ds-PBIs, and s-PBIs (P=0.020, P=0.025, and P=0.001, respectively). With multivariable analyses, the highest apoB/apoAI ratio quartile was associated with PBI (OR, 2.56; 95% CI, 1.39-4.73), ds-PBI (2.48; 1.33-4.62), and advanced (≥ 3) ds-PBIs (2.68; 1.27-5.63) in ICAS group, but not with h-PBI. s-PBI had a dose-response relationship with apoB/apoAI ratio quartiles (6.18; 1.31-29.13 for the second; 5.34; 1.06-26.83 for the third; and 12.17; 2.50-59.19 for the fourth quartile), when referenced to the first quartile. ApoB/apoAI ratio is associated with asymptomatic deep subcortical ischaemic burden as well as with symptomatic lesion in patients with ICAS. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Psychosocial Factors Associated with Subclinical Atherosclerosis in South Asians: The MASALA Study.

PubMed

Shah, Bijal M; Shah, Shriraj; Kandula, Namratha R; Gadgil, Meghana D; Kanaya, Alka M

2016-12-01

South Asians have the highest rates of premature atherosclerotic cardiovascular disease amongst all ethnic groups in the world; however this risk cannot be fully explained by traditional risk factors. Participants from the Mediators of Atherosclerosis in South Asians Living in America Study were included in this cross-sectional analysis. The purpose of this study was to investigate the association of psychosocial factors (including anger, anxiety, depressive symptoms, current and chronic stress, and everyday hassles) with carotid intima-media thickness (CIMT). Three multivariate models were examined to evaluate the association between the psychosocial factors and CIMT. Findings suggest that the impact of psychosocial factors on subclinical atherosclerosis is differential for South Asian men and women. For men, anxiety and depression were associated; while for women, stress was associated with common carotid intima media thickness, independent of traditional CVD risk factors, diet and physical activity.

Association of kidney stones with atherosclerotic cardiovascular disease among adults in the United States: Considerations by race-ethnicity.

PubMed

Glover, LaShaunta M; Bass, Martha Ann; Carithers, Teresa; Loprinzi, Paul D

2016-04-01

There is a paucity of research examining the relationship between kidney stones and risk of cardiovascular disease while considering individuals of different race-ethnicities. The purpose of this study was to examine the association between history of kidney stones and increased odds of atherosclerotic cardiovascular disease (via the Pooled Cohort Equations) across race-ethnicity groups. 5571 participants aged 40-79 from the 2007-2012 cycles of the NHANES were used for this study. A history of kidney stones was collected from survey data. Predicted odds of having a 10-year atherosclerotic cardiovascular disease (ASCVD) event was assessed from the Pooled Cohort Equations. After adjustments, having kidney stones was not associated with an increase odds of having an ASCVD event within the next 10-years (OR 1.03; 95% CI: 0.58-1.82, P=0.91). However, among non-Hispanic blacks, those with kidney stones had a 2.24 increased odds (OR 2.24; 95% CI: 1.08-4.66; P=0.03) of having an ASCVD event within the next 10-years when compared to non-Hispanic blacks with no history of a kidney stone. Kidney stones were associated with 10-year risk of a future ASCVD event among non-Hispanic blacks. Copyright © 2016 Elsevier Inc. All rights reserved.

Selective Imaging of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2 in Atherosclerotic Lesions in Diabetic and Non-diabetic ApoE-/- Mice.

PubMed

Tekabe, Yared; Johnson, Lynne L; Rodriquez, Krissy; Li, Qing; Backer, Marina; Backer, Joseph M

2018-02-01

Plaque vulnerability is associated with inflammation and angiogenesis, processes that rely on vascular endothelial growth factor (VEGF) signaling via two receptors, VEGFR-1 and VEGFR-2. We have recently reported that enhanced uptake of scVEGF-PEG-DOTA/Tc-99m (scV/Tc) single photon emission computed tomography (SPECT) tracer that targets both VEGFR-1 and VEGFR-2, identifies accelerated atherosclerosis in diabetic relative to non-diabetic ApoE -/- mice. Since VEGFR-1 and VEGFR-2 may play different roles in atherosclerotic plaques, we reasoned that selective imaging of each receptor can provide more detailed information on plaque biology. Recently described VEGFR-1 and VEGFR-2 selective mutants of scVEGF, named scVR1 and scVR2, were site-specifically derivatized with Tc-99m chelator DOTA via 3.4 kDa PEG linker, and their selectivity to the cognate receptors was confirmed in vitro. scVR1 and scVR2 conjugates were radiolabeled with Tc-99m to specific activity of 110 ± 11 MBq/nmol, yielding tracers named scVR1/Tc and scVR2/Tc. 34-40 week old diabetic and age-matched non-diabetic ApoE -/- mice were injected with tracers, 2-3 h later injected with x-ray computed tomography (CT) contrast agent and underwent hybrid SPECT/CT imaging. Tracer uptake, localized to proximal aorta and brachiocephalic vessels, was quantified as %ID from. Tracer uptake was also quantified as %ID/g from gamma counting of harvested plaques. Harvested atherosclerotic arterial tissue was used for immunofluorescent analyses of VEGFR-1 and VEGFR-2 and various lineage-specific markers. Focal, receptor-mediated uptake in proximal aorta and brachiocephalic vessels was detected for both scVR1/Tc and scVR2/Tc tracers. Uptake of scVR1/Tc and scVR2/Tc was efficiently inhibited only by "cold" proteins of the same receptor selectivity. Tracer uptake in this area, expressed as %ID, was higher in diabetic vs. non- diabetic mice for scVR1/Tc (p = 0.01) but not for scVR2/Tc. Immunofluorescent analysis

Fracture Risk and Risk Factors for Osteoporosis.

PubMed

Schürer, Christian; Wallaschofski, Henri; Nauck, Matthias; Völzke, Henry; Schober, Hans-Christof; Hannemann, Anke

2015-05-25

As the population ages, diseases of the elderly are becoming more common, including osteoporosis. Ways to assess the risk of fracture and the distribution and effects of known risk factors for osteoporosis will be important in planning for future healthcare needs, as well as in the development of preventive strategies. The study population included 6029 men and women aged 20-90 who underwent examination in the second follow-up wave of the Study of Health in Pomerania (SHIP-2) or in the basal SHIP-Trend Study. The risk of fracture was estimated on the basis of quantitative ultrasonography of the calcaneus. Prior fractures and risk factors for osteoporosis were ascertained in standardized interviews. 4.6% of the male subjects and 10.6% of the female subjects were judged to have an elevated risk of fracture. The corresponding percentages among subjects over age 65 were 8.8% for men and 28.2% for women. Even among subjects under age 55, risk factors for osteoporosis were associated with lower bone stiffness: the mean stiffness index was 103/98 (men/women) without risk factors, 99/96 with one risk factor, and 93/95 with more than one risk factor. Logistic regression analysis yielded an odds ratio of 1.89 (95% confidence interval: 1.44-2.50; p<0.01) for prevalent fractures among subjects aged 75 and older compared to subjects under age 55. The data indicate a high prevalence of osteoporosis from age 65 onward. These findings are consistent with those of other studies from Germany and across Europe. Younger men and women should already begin taking steps to counteract modifiable risk factors.

Cholesterol and prevention of atherosclerotic events: limits of a new frontier.

PubMed

Macedo, Luís Eduardo Teixeira de; E, Faerstein

2017-01-12

Control of atherosclerotic cardiovascular disease - a highly prevalent condition and one of the main causes of mortality in Brazil and worldwide - is a recurrent subject of great interest for public health. Recently, three new guidelines on dyslipidemia and atherosclerosis prevention have been published. The close release of these important publications is a good opportunity for comparison: the Brazilian model has greater sensitivity, the English model does not work with risk stratification, and the American model may be overestimating the risk. This will allow reflection on current progress and identification of controversial aspects which still require further research and debate. It is also an opportunity to discuss issues related to early diagnosis and its efficiency as a preventive strategy for atherosclerotic disease: the transformation of risk into disease, the gradual reduction of cut-off points, the limitations of the screening strategy, and the problem of overdiagnosis. RESUMO O controle da doença cardiovascular aterosclerótica - morbidade de alta prevalência e uma das principais causas de mortalidade no Brasil e no mundo - continua sendo tema de grande interesse para a Saúde Pública. Recentemente, três novas diretrizes sobre dislipidemia e prevenção da aterosclerose foram divulgadas. A convergência no tempo dessas importantes publicações constitui boa oportunidade para sua comparação: o modelo brasileiro tem maior sensibilidade, o inglês não trabalha com risco estratificado e o norte-americano parece estar superestimando o risco.Isso permitirá reflexões acerca dos avanços que já foram alcançados e identificação de aspectos ainda controversos, que seguem exigindo novas pesquisas e debates. É também uma oportunidade para discutir questões relacionadas ao diagnóstico precoce e sua eficiência como estratégia preventiva da doença aterosclerótica: as transformações do risco em doença, a diminuição progressiva de pontos de

Tobacco, illicit drugs use and risk of cardiovascular disease in patients living with HIV.

PubMed

Raposeiras-Roubín, Sergio; Abu-Assi, Emad; Iñiguez-Romo, Andrés

2017-11-01

There is a strong link between HIV, smoking and illicit drugs. This association could be clinically relevant as it may potentiate the risk of cardiovascular diseases (CVD). The purpose of this review is to bring readers up to date on issues concerning the cardiovascular risk associated with tobacco and illicit drugs in patients living with HIV (PLHIV), examining the studies related to this topic published in the last year. There is a strong association between smoking and atherosclerotic disease in PLHIV, reducing life expectancy secondary to CVD by up to 6 years. Illicit drugs were associated with increased risk of atherosclerotic problems but to a lesser extent than smoking. A significant association of drugs such as cocaine with subclinical coronary atherosclerosis been demonstrated. The relation of marijuana, heroin and amphetamines with atherosclerosis generates more controversy. However, those drugs are associated with cardiovascular morbidity, independently of smoking and other traditional risk factors. Tobacco and illicit drugs are linked to CVD in HIV patients. This leads to the need to create special programs to address the addiction to smoking and illicit drugs, in order to mitigate their consequences and reduce cardiovascular risk.

A Comparison between Decision Tree and Random Forest in Determining the Risk Factors Associated with Type 2 Diabetes.

PubMed

Esmaily, Habibollah; Tayefi, Maryam; Doosti, Hassan; Ghayour-Mobarhan, Majid; Nezami, Hossein; Amirabadizadeh, Alireza

2018-04-24

We aimed to identify the associated risk factors of type 2 diabetes mellitus (T2DM) using data mining approach, decision tree and random forest techniques using the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) Study program. A cross-sectional study. The MASHAD study started in 2010 and will continue until 2020. Two data mining tools, namely decision trees, and random forests, are used for predicting T2DM when some other characteristics are observed on 9528 subjects recruited from MASHAD database. This paper makes a comparison between these two models in terms of accuracy, sensitivity, specificity and the area under ROC curve. The prevalence rate of T2DM was 14% among these subjects. The decision tree model has 64.9% accuracy, 64.5% sensitivity, 66.8% specificity, and area under the ROC curve measuring 68.6%, while the random forest model has 71.1% accuracy, 71.3% sensitivity, 69.9% specificity, and area under the ROC curve measuring 77.3% respectively. The random forest model, when used with demographic, clinical, and anthropometric and biochemical measurements, can provide a simple tool to identify associated risk factors for type 2 diabetes. Such identification can substantially use for managing the health policy to reduce the number of subjects with T2DM .

Association of BSG genetic polymorphisms with atherosclerotic cerebral infarction in the Han Chinese population.

PubMed

Zhou, Juan; Song, Bingxin; Duan, Xiaomei; Long, Yuming; Lu, Jinfeng; Li, Zhibin; Zeng, Sian; Zhan, Qiong; Yuan, Mei; Yang, Qidong; Xia, Jian

2014-10-01

The Basigin (BSG, also known as CD147/extracellular matrix metalloproteinase inducer) belongs to the immunoglobulin superfamily (IgSF). It is a cellular receptor for cyclophilin A (CypA), and is originally known as tumor cell collagenase stimulatory factor (TCSF), which could abundantly expressed on the surface of tumor cells, haematopoietic, monocytes, epithelial endothelial cells and smooth muscle cells. Accumulating evidence showed that BSG played an important role in stimulating the secretion of matrix metalloproteinases (MMPs), which has been reported to be involved in the development of atherosclerosis. Since atherosclerosis is an important risk factor for atherosclerotic cerebral infarction (ACI), we speculate that BSG genetic polymorphisms may influence formation of atherosclerosis and then development of ACI. This study aimed to detect the potential association of the single nucleotide polymorphisms (SNP, -631 G > T, -318 G > C, 10141 G > A and 10826 G > A) of BSG gene in Hunan Han Chinese population with ACI. We genotyped 199 ACI patients and 188 matched healthy controls for the four BSG SNP by method of matrix-assisted laser desorption/ionization-time-offlight mass spectrometry (MALDI-TOF MS). Our results suggested that all the polymorphisms were observed in the subjects from Changsha area of Hunan Province. However, no significant difference was observed between the distribution of these SNP in cases and controls. Therefore, we speculate that BSG genetic polymorphisms might not be an important factor in the development of ACI in our Chinese Han population.

Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase: A Potential-Related Gene of Atherosclerosis.

PubMed

Zhou, Mingxue; Ma, Chao; Liu, Weihong; Liu, Hongxu; Wang, Ning; Kang, Qunfu; Li, Ping

2015-09-01

Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a special AT1 antagonist, can dilate blood vessels and reduce blood pressure, but it remained unclear whether valsartan can promote the stability of atherosclerotic plaque by affecting renalase. This study examined the tissue distribution of renalase in ApoE(-/-) mice fed with a high-fat diet and the effect of valsartan on expression of renalase. ApoE(-/-) mice were fed with a high-fat diet for 13 or 26 weeks. As a control, 10 C57BL mice were fed with a standard chow diet. After 13 weeks on the high-fat diet, the ApoE(-/-) mice were randomized (10 mice/group) and treated with valsartan, simvastatin, or distilled water (control group) for an additional 13 weeks accompanied by a high-fat diet. Knockout of ApoE caused a dramatic increase in expression of renalase in mice adipose tissue. With the disturbance of lipid metabolism induced by a high-fat diet, renalase expression decreased in the liver. Renalase can be expressed in smooth muscle cells and M2 macrophages in atherosclerotic plaque, and its expression gradually decreases in the fibrous cap during the transition from stable to vulnerable atherosclerotic plaque. Valsartan, an AT1 receptor antagonist, promotes the stabilization of atherosclerotic plaque by increasing the levels of renalase in serum and the expression of renalase in the fibrous cap of atherosclerotic plaque. It also reduces triglyceride levels in serum and increases the expression of renalase in the liver. Renalase may be a potential-related gene of lipid metabolism and As, and it may be the possible molecular target of valsartan to help stabilize atherosclerotic plaque. © The Author(s) 2015.

Risk factors for cardiovascular disease in subclinical hypothyroidism.

PubMed

Decandia, F

2018-02-01

Subclinical hypothyroidism (SH), defined as an increased serum thyrotropin (TSH) level and normal plasma-free thyroid hormones' concentrations, is common in the general population, in particular, among elderly women. Its prevalence ranges from 4 to 15% and up to 20% among females aged > 60 year. Although SH has been associated with atherosclerotic cardiovascular disease (CVD), it is acknowledged that the high prevalence of dyslipidemia in elderly people is considered a common biochemical condition. Therefore, whether SH is associated with a higher risk for CVD is still controversial. At the moment, no consensus exists on the clinical significance and treatment of the mild form of thyroid failure, although available data suggest that only patients with plasma TSH levels above 10 mU/L may have an increased risk of CVD. However, treatment of SH in older individual requires special consideration with regard to thyroid hormone replacement therapy and expected clinical outcomes, since the increase of TSH observed in this population may represent a physiological process. It is likely that age affects TSH levels, and some studies suggest that modified reference limits for elderly populations should be considered in the diagnosis of mild thyroid failure.

Add-On Effect of Probucol in Atherosclerotic, Cholesterol-Fed Rabbits Treated with Atorvastatin

PubMed Central

Keyamura, Yuka; Nagano, Chifumi; Kohashi, Masayuki; Niimi, Manabu; Nozako, Masanori; Koyama, Takashi; Yasufuku, Reiko; Imaizumi, Ayako; Itabe, Hiroyuki; Yoshikawa, Tomohiro

2014-01-01

Objective Lowering the blood concentration of low-density lipoprotein (LDL) cholesterol is the primary strategy employed in treating atherosclerotic disorders; however, most commonly prescribed statins prevent cardiovascular events in just 30% to 40% of treated patients. Therefore, additional treatment is required for patients in whom statins have been ineffective. In this study of atherosclerosis in rabbits, we examined the effect of probucol, a lipid-lowering drug with potent antioxidative effects, added to treatment with atorvastatin. Methods and Results Atherosclerosis was induced by feeding rabbits chow containing 0.5% cholesterol for 8 weeks. Probucol 0.1%, atorvastatin 0.001%, and atorvastatin 0.003% were administered solely or in combination for 6 weeks, beginning 2 weeks after the start of atherosclerosis induction. Atorvastatin decreased the plasma concentration of non-high-density lipoprotein cholesterol (non-HDLC) dose-dependently; atorvastatin 0.003% decreased the plasma concentration of non-HDLC by 25% and the area of atherosclerotic lesions by 21%. Probucol decreased the plasma concentration of non-HDLC to the same extent as atorvastatin (i.e., by 22%) and the area of atherosclerotic lesions by 41%. Probucol with 0.003% atorvastatin decreased the plasma concentration of non-HDLC by 38% and the area of atherosclerotic lesions by 61%. Co-administration of probucol with atorvastatin did not affect the antioxidative effects of probucol, which were not evident on treatment with atorvastatin alone, such as prevention of in vitro LDL-oxidation, increase in paraoxonase-1 activity of HDL, and decreases in plasma and plaque levels of oxidized-LDL in vivo. Conclusions Probucol has significant add-on anti-atherosclerotic effects when combined with atorvastatin treatment; suggesting that this combination might be beneficial for treatment of atherosclerosis. PMID:24810608

Risk factor profile for atherosclerosis among young adults in Israel--results of a large-scale survey from the young adult periodic examinations in Israel (YAPEIS) database.

PubMed

Sharabi, Y; Grotto, I; Huerta, M; Eldad, A; Green, M S

2001-01-01

Assessing the prevalence of relevant risk factors among young adults is a critical step in the process of preventing atherosclerotic cardiovascular diseases (ASCVD) later in life. The Israel Defense Force Periodic Health Examination Center performs a routine check-up for subjects aged 25-45 years. Medical history, physical examination notes, laboratory results and ECG tracings are recorded, computerized and processed to form the Young Adults Periodic Examinations in Israel (YAPEIS) database. Data representing 31,640 subjects (27,769 males and 3871 females) examined between the years 1991-1999 were analyzed. The prevalence of documented risk factors for ASCVD were evaluated. The results of all parameters were graded categorically as low, moderate or high and the Framingham risk score was calculated. Fifty-one percent of the study participants were found to be overweight (body mass index > or = 25 kg/m2), 8.5% had high systolic blood pressure and 14.6% had high diastolic blood pressure. The prevalence of hypercholesterolemia and hyperglycemia was found to be 44.7 and 9.7%, respectively. Thirty-two percent of the subjects smoked cigarettes, and 76.7% reported not performing any routine physical activity. Furthermore, 31.8% had a Framingham score indicating a greater than 5% risk for developing a coronary event within the next 10 years. As expected, the prevalence of these risk factors increased with age and were found to be less frequent among females. Thus we conclude that many young Israeli adults hold significant risk factors for future ASCVD. Many of these risk factors are modifiable, and risk behavior is often amenable to alteration. Awareness to the high prevalence of risk factors among young adults should spark vigorous health-promotion programs as well as screening, education, and interventional measures aimed at altering the expected outcome of future ASCVD.

An increased waist-to-hip ratio is a key determinant of atherosclerotic burden in overweight subjects.

PubMed

Scicali, Roberto; Rosenbaum, David; Di Pino, Antonino; Giral, Philippe; Cluzel, Philippe; Redheuil, Alban; Piro, Salvatore; Rabuazzo, Agata Maria; Purrello, Francesco; Bruckert, Eric; Gallo, Antonio

2018-04-21

The association of overweight status and cardiovascular disease is not clear. In this study we aimed to investigate coronary atherosclerotic disease, evaluated as coronary artery calcium score (CACs), in overweight patients with or without abdominal obesity as defined by waist-to-hip ratio (WHR). We enrolled 276 patients aged between 40 and 70 years, with a body mass index of 25-29.9 kg/m 2 and at least one cardiovascular risk factor. Exclusion criteria were history of diabetes, cardiovascular or renal disease. Patients were stratified in high WHR (H-WHR) or low WHR (L-WHR) group according to WHR (≥ 0.85 for women and ≥ 0.90 for men) and underwent multi-detector computed tomography for CACs. Mean carotid intima-media thickness (IMT) and plaque presence were equally assessed. CACs was higher in the H-WHR group compared to L-WHR (9.05 [0.0-83.48] vs 0.0 [0.0-64.7] AU, p < 0.01); the prevalence of CACs > 0 in the H-WHR group was significantly higher than subjects with L-WHR (59.6% vs 38.5%, p < 0.001). Moreover, H-WHR group had higher mean IMT (0.64 [0.56-0.72] vs 0.59 [0.55-0.67] mm, p < 0.05) and higher carotid plaque prevalence (63.7% vs 50.8%, p < 0.05) compared to subjects with L-WHR. Logistic regression showed that H-WHR was associated with presence of CACs and carotid plaque (p < 0.01). In a multiple linear regression, WHR was positively associated with CACs and IMT (p < 0.01). H-WHR is a marker of coronary and peripheral atherosclerotic burden in overweight patients.

Chronic exposure to biomass fuel is associated with increased carotid artery intima-media thickness and a higher prevalence of atherosclerotic plaque

PubMed Central

Painschab, Matthew S; Davila-Roman, Victor G; Gilman, Robert H; Vasquez-Villar, Angel D; Pollard, Suzanne L; Wise, Robert A; Miranda, J Jaime; Checkley, William

2015-01-01

Background Biomass fuels are used for cooking in the majority of rural households worldwide. While their use is associated with an increased risk of lung diseases and all-cause mortality, the effects on cardiovascular disease (CVD) are not well characterised. Exposure to biomass fuel smoke has been associated with lung-mediated inflammation and oxidative stress, which may increase the risk of atherosclerosis as evaluated by carotid intima-media thickness (CIMT), carotid atherosclerotic plaque prevalence and blood pressure. Methods A cross-sectional study was performed in 266 adults aged ≥35 years in Puno, Peru (3825 m above sea level). We stratified participants by their long-term history of exposure to clean fuel (n=112) or biomass fuel (n=154) and measured 24 h indoor particulate matter (PM2.5) in a random subset (n=84). Participants completed questionnaires and underwent a clinical assessment, laboratory analyses and carotid artery ultrasound. The main outcome measures were CIMT, carotid plaque and blood pressure. Results The groups were similar in age and gender. The biomass fuel group had greater unadjusted mean CIMT (0.66 vs 0.60 mm; p<0.001), carotid plaque prevalence (26% vs 14%; p=0.03), systolic blood pressure (118 vs 111 mm Hg; p<0.001) and median household PM2.5 (280 vs 14 μg/m3; p<0.001). In multivariable regression, the biomass fuel group had greater mean CIMT (mean difference=0.03 mm, 95% CI 0.01 to 0.06; p=0.02), a higher prevalence of carotid plaques (OR=2.6, 95% CI 1.1 to 6.0; p=0.03) and higher systolic blood pressure (mean difference=9.2 mm Hg, 95% CI 5.4 to 13.0; p<0.001). Conclusions Chronic exposure to biomass fuel was associated with increased CIMT, increased prevalence of atherosclerotic plaques and higher blood pressure. These findings identify biomass fuel use as a risk factor for CVD, which may have important global health implications. PMID:23619984

Association between kidney function and genetic polymorphisms in atherosclerotic and chronic kidney diseases: A cross-sectional study in Japanese male workers

PubMed Central

Nakatochi, Masahiro; Yasuda, Yoshinari; Honda, Hiroyuki; Kuwatsuka, Yachiyo; Kato, Sawako; Kikuchi, Kyoko; Kondo, Takaaki; Iwata, Masamitsu; Nakashima, Toru; Yasui, Hiroshi; Takamatsu, Hideki; Okajima, Hiroshi; Yoshida, Yasuko; Maruyama, Shoichi

2017-01-01

Background Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD. Methods We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated. Results In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with P value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1 rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09–1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively). Conclusions After adjustment for clinical factors, kidney function was associated with BRAP rs3782886 and SPATA5L1 rs

Association between kidney function and genetic polymorphisms in atherosclerotic and chronic kidney diseases: A cross-sectional study in Japanese male workers.

PubMed

Kubo, Yoko; Imaizumi, Takahiro; Ando, Masahiko; Nakatochi, Masahiro; Yasuda, Yoshinari; Honda, Hiroyuki; Kuwatsuka, Yachiyo; Kato, Sawako; Kikuchi, Kyoko; Kondo, Takaaki; Iwata, Masamitsu; Nakashima, Toru; Yasui, Hiroshi; Takamatsu, Hideki; Okajima, Hiroshi; Yoshida, Yasuko; Maruyama, Shoichi

2017-01-01

Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD. We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated. In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with P value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1 rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09-1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively). After adjustment for clinical factors, kidney function was associated with BRAP rs3782886 and SPATA5L1 rs2467853 and the GRS for CKD that we

Role of infrasound pressure waves in atherosclerotic plaque rupture: a theoretical approach.

PubMed

Tsatsaris, Athanasios; Koukounaris, Efstathios; Motsakos, Theodoros; Perrea, Despina

2007-01-01

To investigate the role of infrasound aortic pressure waves (IPW) in atherosclerotic plaque rupture. Atherosclerotic plaques have been simulated partly, in two dimensions, as being short or long Conical Intersections (CIS), that is to say elliptic, parabolic or hyperbolic surfaces. Consequently, the course and reflection of the generated aortic pressure wave (infrasound domain-less than 20Hz) has been examined around the simulated plaques. The incidence of IPW on plaque surface results both in reflection and "refraction" of the wave. The IPW course within tissue, seems to be enhanced by high Cu-level presence at these areas according to recent evidence (US2003000388213). The "refracted", derived wave travels through plaque tissue and is eventually accumulated to the foci of the respective CIS-plaque geometry. The foci location within or underneath atheroma declares zones where infrasound energy is mostly absorbed. This process, among other mechanisms may contribute to plaque rupture through the development of local hemorrhage and inflammation in foci areas. In future, detection of foci areas and repair (i.e. via Laser Healing Microtechnique) may attenuate atherosclerotic plaque rupture behavior.

Cardiac risk stratification: Role of the coronary calcium score

PubMed Central

Sharma, Rakesh K; Sharma, Rajiv K; Voelker, Donald J; Singh, Vibhuti N; Pahuja, Deepak; Nash, Teresa; Reddy, Hanumanth K

2010-01-01

Coronary artery calcium (CAC) is an integral part of atherosclerotic coronary heart disease (CHD). CHD is the leading cause of death in industrialized nations and there is a constant effort to develop preventative strategies. The emphasis is on risk stratification and primary risk prevention in asymptomatic patients to decrease cardiovascular mortality and morbidity. The Framingham Risk Score predicts CHD events only moderately well where family history is not included as a risk factor. There has been an exploration for new tests for better risk stratification and risk factor modification. While the Framingham Risk Score, European Systematic Coronary Risk Evaluation Project, and European Prospective Cardiovascular Munster study remain excellent tools for risk factor modification, the CAC score may have additional benefit in risk assessment. There have been several studies supporting the role of CAC score for prediction of myocardial infarction and cardiovascular mortality. It has been shown to have great scope in risk stratification of asymptomatic patients in the emergency room. Additionally, it may help in assessment of progression or regression of coronary artery disease. Furthermore, the CAC score may help differentiate ischemic from nonischemic cardiomyopathy. PMID:20730016

Association of dietary nitrate with atherosclerotic vascular disease mortality: a prospective cohort study of older adult women.

PubMed

Blekkenhorst, Lauren C; Bondonno, Catherine P; Lewis, Joshua R; Devine, Amanda; Woodman, Richard J; Croft, Kevin D; Lim, Wai H; Wong, Germaine; Beilin, Lawrence J; Prince, Richard L; Hodgson, Jonathan M

2017-07-01

Background: Nitrate-rich vegetables lower blood pressure and improve endothelial function in humans. It is not known, however, whether increased consumption of nitrate-rich vegetables translates to a lower risk of atherosclerotic vascular disease (ASVD) mortality. Objective: The objective was to investigate the association of nitrate intake from vegetables with ASVD mortality. Design: A total of 1226 Australian women aged 70-85 y without prevalent ASVD and/or diabetes were recruited in 1998 and were studied for 15 y. We assessed demographic and ASVD risk factors at baseline (1998), and we used a validated food-frequency questionnaire to evaluate dietary intake. Nitrate intake from vegetables was calculated by use of a newly developed comprehensive database. The primary outcome was any death attributed to ASVD ascertained by using linked data that were provided via the Western Australian Data Linkage system. We used Cox proportional hazards modeling to examine the association between nitrate intake and ASVD mortality before and after adjustment for lifestyle and cardiovascular disease risk factors. Results: During a follow-up period of 15,947 person-years, 238 of 1226 (19.4%) women died of ASVD-related causes. The mean ± SD vegetable nitrate intake was 67.0 ± 29.2 mg/d. Each SD higher vegetable nitrate intake was associated with a lower risk of ASVD mortality in both unadjusted [HR: 0.80 (95% CI: 0.70, 0.92), P = 0.002] and multivariable-adjusted [HR: 0.79 (95% CI: 0.68, 0.93), P = 0.004] analyses. This relation was attenuated after further adjustment for diet quality [HR: 0.85 (95% CI: 0.72, 1.01), P = 0.072]. Higher vegetable nitrate intake (per SD) also was associated with a lower risk of all-cause mortality [multivariable-adjusted HR: 0.87 (95% CI: 0.78, 0.97), P = 0.011]. Conclusions: Nitrate intake from vegetables was inversely associated with ASVD mortality independent of lifestyle and cardiovascular disease risk factors in this population of older adult

Correlation of calcified carotid plaques detected by panoramic radiograph with risk factors for stroke development.

PubMed

Griniatsos, John; Damaskos, Spyros; Tsekouras, Nikolaos; Klonaris, Chris; Georgopoulos, Sotirios

2009-10-01

The aim was to evaluate whether patients with calcifications in the carotid region detectable by panoramic radiograph differ in the prevalence of risk factors for stroke development compared with those without calcifications. Forty consecutive individuals suffering from proven carotid artery atherosclerotic occlusive disease were submitted to carotid endarterectomy. Seventeen patients were symptomatic at the time of referral, having suffered at least 1 episode of ischemic cerebral event during the preceding 6 months, mainly transient ischemic attacks or amaurosis fugax, and the remaining 23 patients were asymptomatic and the diagnosis was reached during a thorough investigation of coexisting coronary or peripheral vascular disease. Preoperatively, all patients had undergone panoramic radiograph examination, as the presurgical protocol commanded. Based on the panoramic radiograph results, patients in whom calcifications were detected either unilaterally (n = 10) or bilaterally (n = 18) constituted group A (n = 28) and patients in whom no calcifications were detected constituted group B (n = 12) of this study. Univariate analysis among several risk factors for stroke development between the 2 groups of patients disclosed a stastistically significant lower incidence of diabetes mellitus (P = .005) but a higher incidence of symptomatic plaques (P < .030) in the group of patients with detectable calcifications in the panoramic radiograph. Patients with calcified carotid plaques detectable by panoramic radiography are more likely to have suffered cerebrovascular events. Therefore, patients with detectable carotid plaque in panoramic radiographs require referral to their physician for further investigation.

The Kaiser Permanente Northwest Cardiovascular Risk Factor Management Program: A Model for All

PubMed Central

Joyce, Jodi S; Fetter, Martina M; Klopfenstein, Dean H; Nash, Michael K

2005-01-01

Proof of the effectiveness of preventive measures that reduce established risk traits for atherothrombotic disorders has spurred attempts to systematically apply these interventions among susceptible populations. One such attempt is the Cardiovascular Risk Factor Management (CVRFM) Program, launched in 2003 to optimize clinical management and outcomes for 75,000 Kaiser Permanente Northwest Region (KPNW) members with atherosclerotic cardiovascular disease (CVD) or hypertension. The CVRFM Program is a centralized, multidisciplinary, proactive telephone-based clinical management intervention consisting of an “outreach” call, an interview, a mailed individualized care plan and information packet, regular follow-up (including protocolized medication management) and—when “goal status” is achieved—transfer of the patient to a maintenance plan. Quarterly evaluation of effectiveness entailed measurement of a range of clinical, utilization, and member satisfaction outcomes. Results by the fourth quarter were outstanding: For example, >98% of participants with coronary disease or diabetes had LDL cholesterol testing, >90% of coronary patients received aspirin or statin treatment, 99% were “extremely” or “very” satisfied with the program, and reductions were observed in the number of hospitalizations and visits to the emergency department and clinic. Mathematical models predict a decrease in myocardial infarctions and cardiovascular mortality within two years after implementing the program, the underlying principles of which should yield similar improvement in other Kaiser Permanente (KP) Regions and in other health care organizations. PMID:21660155

Risk behaviours among early adolescents: risk and protective factors.

PubMed

Wang, Ruey-Hsia; Hsu, Hsiu-Yueh; Lin, Shu-Yuan; Cheng, Chung-Ping; Lee, Shu-Li

2010-02-01

This paper is a report of a study conducted to examine the influence of risk/protective factors on risk behaviours of early adolescents and whether protective factors moderate their impact. An understanding of how risk and protective factors operate to influence risk behaviours of early adolescents will better prepare nurses to perform interventions appropriately to reduce risk behaviours of early adolescents. A cross-sectional study was carried out, based on a sample of public junior high schools (from 7th to 9th grades) in one city and one county in Taiwan. An anonymous questionnaire designed to measure five risk factors, six protective factors and risk behaviours was administered from October 2006 to March 2007. Data from 878 students were used for the present analysis. Pearson's correlations, anova with random effect models, and generalized linear models were used to analyse the statistically significant explanatory variables for risk behaviours. Gender, perceived father's risk behaviour, perceived mother's risk behaviour, health self-efficacy, interaction of health self-efficacy and perceived peers' risk behaviour, and interaction of emotional regulation and perceived peers' risk behaviour were statistically significant explanatory variables of risk behaviours. Health self-efficacy and emotional regulation moderated the negative effects of peers' perceived risk behaviour on risk behaviours. All protective factors were negative statistically correlated with risk behaviours, and all risk factors positively statistically correlated with risk behaviours. Male adolescents should be considered an at-risk group for risk behaviour intervention. Nurses could provide early adolescents with training regarding health self-efficacy improvement, self-esteem enhancement, emotional regulation skills to reduce their risk behaviours.

Risk factors for stress fractures.

PubMed

Bennell, K; Matheson, G; Meeuwisse, W; Brukner, P

1999-08-01

Preventing stress fractures requires knowledge of the risk factors that predispose to this injury. The aetiology of stress fractures is multifactorial, but methodological limitations and expediency often lead to research study designs that evaluate individual risk factors. Intrinsic risk factors include mechanical factors such as bone density, skeletal alignment and body size and composition, physiological factors such as bone turnover rate, flexibility, and muscular strength and endurance, as well as hormonal and nutritional factors. Extrinsic risk factors include mechanical factors such as surface, footwear and external loading as well as physical training parameters. Psychological traits may also play a role in increasing stress fracture risk. Equally important to these types of analyses of individual risk factors is the integration of information to produce a composite picture of risk. The purpose of this paper is to critically appraise the existing literature by evaluating study design and quality, in order to provide a current synopsis of the known scientific information related to stress fracture risk factors. The literature is not fully complete with well conducted studies on this topic, but a great deal of information has accumulated over the past 20 years. Although stress fractures result from repeated loading, the exact contribution of training factors (volume, intensity, surface) has not been clearly established. From what we do know, menstrual disturbances, caloric restriction, lower bone density, muscle weakness and leg length differences are risk factors for stress fracture. Other time-honoured risk factors such as lower extremity alignment have not been shown to be causative even though anecdotal evidence indicates they are likely to play an important role in stress fracture pathogenesis.

A Quantitative Model of Early Atherosclerotic Plaques Parameterized Using In Vitro Experiments.

PubMed

Thon, Moritz P; Ford, Hugh Z; Gee, Michael W; Myerscough, Mary R

2018-01-01

There are a growing number of studies that model immunological processes in the artery wall that lead to the development of atherosclerotic plaques. However, few of these models use parameters that are obtained from experimental data even though data-driven models are vital if mathematical models are to become clinically relevant. We present the development and analysis of a quantitative mathematical model for the coupled inflammatory, lipid and macrophage dynamics in early atherosclerotic plaques. Our modeling approach is similar to the biologists' experimental approach where the bigger picture of atherosclerosis is put together from many smaller observations and findings from in vitro experiments. We first develop a series of three simpler submodels which are least-squares fitted to various in vitro experimental results from the literature. Subsequently, we use these three submodels to construct a quantitative model of the development of early atherosclerotic plaques. We perform a local sensitivity analysis of the model with respect to its parameters that identifies critical parameters and processes. Further, we present a systematic analysis of the long-term outcome of the model which produces a characterization of the stability of model plaques based on the rates of recruitment of low-density lipoproteins, high-density lipoproteins and macrophages. The analysis of the model suggests that further experimental work quantifying the different fates of macrophages as a function of cholesterol load and the balance between free cholesterol and cholesterol ester inside macrophages may give valuable insight into long-term atherosclerotic plaque outcomes. This model is an important step toward models applicable in a clinical setting.

Quantification of carotid atherosclerotic plaque components using feature space analysis and magnetic resonance imaging.

PubMed

Karmonik, Christof; Basto, Pamela; Morrisett, Joel D

2006-01-01

Atherosclerosis is one of the main causes of cardiovascular disease, accounting for more than one third of all deaths in the United States, there is a growing need to develop non-invasive techniques to assess the severity of atherosclerotic plaque burden. Recent research has suggested that not the size of the atherosclerotic plaque but rather its composition is indicative for plaque rupture as the underlying event of stroke and acute coronary syndrome. With its excellent soft-tissue contrast, magnetic resonance imaging (MRI) is a favored modality for examining plaque composition. In an ex-vivo study, aimed to show the feasibility of quantifying the components of carotid atherosclerotic plaques in-vivo, we acquired multi-contrast MRI images of 13 freshly excised endarterectomy tissues with commercially available MRI sequences and a human surface coil. Feature space analysis (FSA) was utilized in four representative tissues to determine the total relative abundance of calcific, lipidic, fibrotic, thrombotic and normal components as well as in consecutive 2 mm sections across the carotid bifurcation in each tissue. Excellent qualitative agreement between the FSA results and the results obtained from histological methods was observed. This study demonstrates the feasibility of combining MRI with FSA to quantify carotid atherosclerotic plaques in-vivo.

Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression.

PubMed

Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

2015-08-01

Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte recruitment during atherosclerotic plaque progression. Systemic IgE-mediated mast cell activation in apoE(-/-)μMT mice resulted in an increase in atherosclerotic lesion size as compared to control mice, and interestingly, the number of neutrophils was highly increased in these lesions. In addition, peritoneal mast cell activation led to a massive neutrophil influx into the peritoneal cavity in C57Bl6 mice, whereas neutrophil numbers in mast cell deficient Kit(W(-sh)/W(-sh)) mice were not affected. Within the newly recruited neutrophil population, increased levels of CXCR2(+) and CXCR4(+) neutrophils were observed after mast cell activation. Indeed, mast cells were seen to contain and release CXCL1 and CXCL12, the ligands for CXCR2 and CXCR4. Intriguingly, peritoneal mast cell activation in combination with anti-CXCR2 receptor antagonist resulted in decreased neutrophil recruitment, thus establishing a prominent role for the CXCL1/CXCR2 axis in mast cell-mediated neutrophil recruitment. Our data suggest that chemokines, and in particular CXCL1, released from activated mast cells induce neutrophil recruitment to the site of inflammation, thereby aggravating the ongoing inflammatory response and thus affecting plaque progression and destabilization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Quantitative evaluation of lipid concentration in atherosclerotic plaque phantom by near-infrared multispectral angioscope at wavelengths around 1200 nm

NASA Astrophysics Data System (ADS)

Matsui, Daichi; Ishii, Katsunori; Awazu, Kunio

2015-07-01

Atherosclerosis is a primary cause of critical ischemic diseases like heart infarction or stroke. A method that can provide detailed information about the stability of atherosclerotic plaques is required. We focused on spectroscopic techniques that could evaluate the chemical composition of lipid in plaques. A novel angioscope using multispectral imaging at wavelengths around 1200 nm for quantitative evaluation of atherosclerotic plaques was developed. The angioscope consists of a halogen lamp, an indium gallium arsenide (InGaAs) camera, 3 optical band pass filters transmitting wavelengths of 1150, 1200, and 1300 nm, an image fiber having 0.7 mm outer diameter, and an irradiation fiber which consists of 7 multimode fibers. Atherosclerotic plaque phantoms with 100, 60, 20 vol.% of lipid were prepared and measured by the multispectral angioscope. The acquired datasets were processed by spectral angle mapper (SAM) method. As a result, simulated plaque areas in atherosclerotic plaque phantoms that could not be detected by an angioscopic visible image could be clearly enhanced. In addition, quantitative evaluation of atherosclerotic plaque phantoms based on the lipid volume fractions was performed up to 20 vol.%. These results show the potential of a multispectral angioscope at wavelengths around 1200 nm for quantitative evaluation of the stability of atherosclerotic plaques.

Perceived work-related stress and early atherosclerotic changes in healthy employees.

PubMed

Bugajska, Joanna; Widerszal-Bazyl, Maria; Radkiewicz, Piotr; Pasierski, Tomasz; Szulczyk, Grazyna Anna; Zabek, Jakub; Wojciechowska, Bozena; Jedryka-Góral, Anna

2008-08-01

This study was conducted to investigate the relationship between perceived work-related stress and preclinical atherosclerosis. A total of 100 managers and 50 office workers aged 35-65 participated in a questionnaire study. Individual, family and work-related stress risk factors and coping were evaluated in all the studied individuals. Serum levels of biochemical (total cholesterol, LDL, HDL, TG, glucose) and serological risk factors of atherosclerosis (anticardiolipin, anti-beta(2) GPI, anti-oxLDL, anti-HSP and anti-hsCRP antibodies) were evaluated. A computer analysis of B-mode ultrasound images was used to assess carotid artery intima-media thickness (IMT) and atherosclerotic plaque in carotid arteries. Statistical analysis was conducted with SPSS v. 11.5. The studied individuals showed average ranges of both the global stress level and of coping results. In 71% no changes were found in the ultrasound image and in 29% of individuals (43) the presence of plaque was shown. The mean value of the IMT measure was 0.0618 +/- 0.013 mm. IMT and plaque correlated negatively with the level of global work-related stress (r = -0.26; P < 0.01; and r = -0.28; P < 0.01; respectively). No correlation was found either between work-related stress and coping, or between coping and IMT (P > 0.05), or between work-related stress and healthy lifestyle (no smoking, no excessive use of alcohol, high physical activity), or between healthy lifestyle and IMT (P > 0.05). Positive correlation between IMT and LDL and smoking did not result from higher stress reaction in the studied individuals. The explanation of the negative correlation between perceived work-related stress and preclinical atherosclerosis was not confirmed either by the subjects under high stress undertaking healthy protective activities or by their escaping into unhealthy behaviour. The most probable interpretation of the results is that in individuals with a low level of perceived work-related stress, somatization of

Anti-atherosclerotic effect of Fermentum Rubrum and Gynostemma pentaphyllum mixture in high-fat emulsion- and vitamin D3-induced atherosclerotic rats.

PubMed

Gou, San-Hu; Liu, Bei-Jun; Han, Xiu-Feng; Wang, Li; Zhong, Chao; Liang, Shan; Liu, Hui; Qiang, Yin; Zhang, Yun; Ni, Jing-Man

2018-05-01

The mixture of Hongqu and gypenosides (HG) is composed of Fermentum Rubrum (Hongqu, in Chinese) and total saponins of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, in Chinese) in a 3.6:1 weight ratio. Both Hongqu and Jiaogulan are considered valuable traditional Chinese medicines (TCMs); they have been commonly used in China for the treatment of hyperlipidemia and related diseases for centuries. The aim of the current study was assess the anti-atherosclerotic effect of HG. Sixty-four Wistar rats were randomly divided into eight groups: normal, model, positive control (simvastatin, 1 mg/kg), Hongqu-treated (72 mg/kg), gypenoside (total saponin)-treated (20 mg/kg), and three doses HG-treated (50, 100, and 200 mg/kg). All of the rats were fed a basal diet. Additionally, the model group rats were intragastrically administered a high-fat emulsion and intraperitoneally injected with vitamin D 3 . The serum lipid profiles, oxidative stress, inflammatory cytokine, and hepatic antioxidant levels were then determined. Furthermore, the liver histopathology and arterial tissue were analyzed, and the expression of hyperlipidemia- and atherosclerosis (AS)-related genes was measured using reverse transcription-polymerase chain reaction. The AS rat model was established after 80 days. Compared to the model group, the HG-treated groups showed an obvious improvement in the serum lipid profiles, oxidative stress, and inflammatory cytokine levels, and showed markedly increased hepatic total antioxidant capacity. Moreover, the expression of genes related to lipid synthesis and inflammation reduced and that of the genes related to lipid oxidation increased in the liver and arterial tissue, which also reflected an improved health condition. the anti-atherosclerotic effects of HG were superior to those of simvastatin, Hongqu, and the gypenosides. Therefore, HG may be a useful anti-atherosclerotic TCM preparation. Copyright © 2017. Published by Elsevier Taiwan LLC.

Connecting the Lines between Hypogonadism and Atherosclerosis

PubMed Central

Fahed, Akl C.; Gholmieh, Joanna M.; Azar, Sami T.

2012-01-01

Epidemiological studies show that atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide and point to gender differences with ageing males being at highest risk. Atherosclerosis is a complex process that has several risk factors and mediators. Hypogonadism is a commonly undiagnosed disease that has been associated with many of the events, and risk factors leading to atherosclerosis. The mechanistic relations between testosterone levels, atherosclerotic events, and risk factors are poorly understood in many instances, but the links are clear. In this paper, we summarize the research journey that explains the link between hypogonadism, each of the atherosclerotic events, and risk factors. We look into the different areas from which lessons could be learned, including epidemiological studies, animal and laboratory experiments, studies on androgen deprivation therapy patients, and studies on testosterone-treated patients. We finish by providing recommendations for the clinician and needs for future research. PMID:22518131

Salivary Gland Cancer: Risk Factors

MedlinePlus

... Cancer: Risk Factors Request Permissions Salivary Gland Cancer: Risk Factors Approved by the Cancer.Net Editorial Board , ... To see other pages, use the menu. A risk factor is anything that increases a person’s chance ...

Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study.

PubMed

López-Cancio, Elena; Galán, Amparo; Dorado, Laura; Jiménez, Marta; Hernández, María; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Barallat, Jaume; Massuet, Anna; Alzamora, Maria Teresa; Dávalos, Antonio; Arenillas, Juan Francisco

2012-10-01

Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease. Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular

Serum uric acid level is an independent risk factor for presence of calcium in coronary arteries: an observational case-controlled study.

PubMed

Atar, Aslı Inci; Yılmaz, Omer Cağlar; Akın, Kayıhan; Selçoki, Yusuf; Er, Okan; Eryonucu, Beyhan

2013-03-01

A link between uric acid levels and cardiovascular diseases has been previously reported. Coronary artery calcium score (CACS) is a marker of atherosclerotic disease and a predictor of cardiovascular events. We sought to determine if serum uric acid level is an independent risk factor for the presence of calcium in coronary arteries. Four hundred and forty-two patients who were evaluated in the cardiology outpatient clinic for suspected coronary heart disease with a low-moderate risk for coronary artery disease were included in this observational case-controlled study. Serum uric acid levels were measured with colorimetric methods. CACS were performed using a 64-slice CT scanner. Patients were divided to 3 groups according to their CACS value (Group 1: CACS=0, Group 2: CACS 1-100, Group 3: CACS>100). The demographical characteristics and laboratory findings of 3 groups were similar, except age, fasting glucose levels and serum uric acid levels. Serum uric acid levels were found to increase significantly with increasing CACS (p=0.001). Patients were grouped according to presence CAC (CACS=0 and CACS≥1) and in the multiple regression analysis, age (OR, 1.11, 95% CI, 1.07-1.16), smoking (OR, 3.83, 95% CI, 2.06-7.09), serum uric acid levels (OR, 1.26, 95% CI, 1.04-1.54) and average 10-year total risk of Framingham risk score (OR, 1.13, 95% CI, 1.04-1.09) appeared as independent factors predictive of presence of CAC (p<0.05). Serum uric acid level is an independent risk factor for presence of coronary calcium. Moreover, increasing levels of serum uric acid are associated with increasing CACS.

The Leu72Met polymorphism of the ghrelin gene is associated with a decreased risk for type 2 diabetes.

PubMed

Berthold, Heiner K; Giannakidou, Eleni; Krone, Wilhelm; Mantzoros, Christos S; Gouni-Berthold, Ioanna

2009-01-01

Ghrelin is involved in several metabolic and cardiovascular processes. The Leu72Met polymorphism of its gene was associated with an increased risk of type 2 diabetes (DM2) in some, but not all studies. Its association with atherosclerosis is not known. We investigated 420 Caucasian subjects with DM2 and 430 controls without diabetes (56.6% male, age 62+/-10 years). The Leu72Leu genotype frequencies were 89.76/84.65%, the Leu72Met 9.52/15.12% and the Met72Met 0.71/0.23% (P=0.029) in the DM2 and controls groups, respectively. In subjects with Met72+ genotypes the risk of DM2 was significantly decreased (univariate OR 0.63, 95% CI 0.42-0.95, P=0.026). In a logistic regression model, body mass index, hypertension and a positive family history for diabetes were predictors of diabetes while the polymorphism remained negatively associated with the disease (OR 0.62, 95% CI 0.40-0.97, P=0.036). After adjusting for known risk factors for atherosclerosis, the Met72+ variant was not associated with atherosclerotic disease (OR 1.41, 95% CI 0.78-2.54, P=0.25). Ghrelin concentrations were not associated with the polymorphism, DM2 or atherosclerotic disease. The Leu72Met polymorphism of the ghrelin gene is associated with a decreased risk for DM2. There is no association between the variant and atherosclerotic disease or ghrelin concentrations.

Prevalence of Systemic Atherosclerosis Burdens and Overlapping Stroke Etiologies and Their Associations With Long-term Vascular Prognosis in Stroke With Intracranial Atherosclerotic Disease.

PubMed

Hoshino, Takao; Sissani, Leila; Labreuche, Julien; Ducrocq, Gregory; Lavallée, Philippa C; Meseguer, Elena; Guidoux, Céline; Cabrejo, Lucie; Hobeanu, Cristina; Gongora-Rivera, Fernando; Touboul, Pierre-Jean; Steg, Philippe Gabriel; Amarenco, Pierre

2018-02-01

Patients who have experienced stroke with intracranial atherosclerotic disease (ICAD) may also have concomitant atherosclerosis in different arterial beds and other possible causes for ischemic stroke. However, little is known about the frequency and prognostic effect of such overlapping diseases. To describe the prevalence of systemic atherosclerotic burdens and overlapping stroke etiologies and their contributions to long-term prognoses among patients who have experienced stroke with ICAD. The Asymptomatic Myocardial Ischemia in Stroke and Atherosclerotic Disease study is a single-center prospective study in which 405 patients with acute ischemic stroke within 10 days of onset were consecutively enrolled between June 2005 and December 2008 and followed up for 4 years. After excluding 2 patients because of incomplete investigations, 403 were included in this analysis. Significant ICAD was defined as having 50% or greater stenosis/occlusion by contrast-enhanced/time-of-flight magnetic resonance angiography, computed tomography angiography, and/or transcranial Doppler ultrasonography. Systemic vascular investigations on atherosclerotic disease were performed with ultrasonography in carotid arteries, aorta and femoral arteries, and by angiography in coronary arteries. Coexistent stroke etiologies were assessed using the atherosclerosis, small-vessel disease, cardiac pathology, other cause, and dissection (ASCOD) grading system. We estimated the 4-year risk of major adverse cardiovascular events (MACE), including vascular death, nonfatal cardiac events, nonfatal stroke, and major peripheral arterial events. Of 403 participants, 298 (74%) were men and the mean (SD) age was 62.6 (13.1) years. Significant ICAD was found in 146 (36.2%). Patients with significant ICAD more often had aortic arch (70 [60.9%] vs 99 [49.0%]; P = .04) and coronary artery (103 [76.9%] vs 153 [63.2%]; P = .007) atherosclerosis than those without. Among patients with ICAD, concurrent

High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

NASA Astrophysics Data System (ADS)

Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

2016-02-01

Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy

PubMed Central

Rossouw, Jacques E; Johnson, Karen C; Pettinger, Mary; Cushman, Mary; Sandset, Per Morten; Kuller, Lewis; Rosendaal, Frits; Rosing, Jan; Wasserthal-Smoller, Sylvia; Martin, Lisa W; Manson, JoAnn E; Lakshminarayan, Kamakshi; Merino, Jose G; Lynch, John

2012-01-01

Background and Purpose To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized APC resistance ratio, nAPCsr) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy (PHT). Methods Nested case-control study of 455 cases of ischemic stroke and 565 matched controls in the Women’s Health Initiative trials of PHT. Results Baseline free TFPI was associated with ischemic stroke risk, OR (95% CI) per SD increase = 1.17 (1.01, 1.37, p=0.039, but baseline nAPCsr was not, OR per SD increase = 0.89 (0.75, 1.05), p=0.15. Baseline TFPI levels and nAPCsr did not modify the effect of PHT on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction p = 0.452 and 0.971 respectively). In subgroup analyses baseline nAPCsr was inversely associated with lacunar strokes, OR per SD increase = 0.74 (0.57, 0.96), p=0.025, and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes, p=0.008. Conclusions Pro-coagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to PHT. PMID:22363056

Risk Factor Assessment Branch (RFAB)

Cancer.gov

The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

Cardiovascular risk factors and dementia.

PubMed

Fillit, Howard; Nash, David T; Rundek, Tatjana; Zuckerman, Andrea

2008-06-01

Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.

Prevalence of cardiovascular disease risk factors among pharmacy students from Wroclaw Medical University (Poland).

PubMed

Ilow, Rafał; Różańska, Dorota; Regulska-Ilow, Bożena

2017-08-01

Atherosclerotic processes begin in childhood and their development worsens during adolescence. Early prevention of CVD risk factors may have an important impact on the future health of young people. It can be also helpful in reducing the costs of treating CVD later in life. The aim of this study was to assess the prevalence of selected cardiovascular disease risk factors among pharmacy students. The study group consisted of 1,168 pharmacy students (892 women and 276 men) from Wroclaw Medical University. The average age was 22.9 years among women and 23.2 years among men. This cross-sectional study was conducted between 2004-2012. 27.5% of men and 7.1% of women were found to be overweight, while visceral obesity was found in 15.2% and in 10.1% of students, respectively. Hypertension was diagnosed in 27.2% of men and in 7.8% of women. Low physical activity was declared by 41.9% of women and by 31.9% of men. There were 22.1% of men and 10% of women who were current smokers. The majority of the study group did not consume enough fruits and vegetables (women 61.8%, men 75%). Body mass index (BMI) was positively associated with waist and hip measurements, waist-to-hip ratio (WHR) and body fat percentage, while blood pressure was positively associated with BMI and waist circumference. It was found that men with high physical activity had lower BMIs, body fat percentage, waist and hip circumferences, WHR, diastolic blood pressure and heart rate than those who declared low physical activity. Comparing women with high physical activity to those with low physical activity, only lower heart rate was observed. A higher prevalence of cardiovascular risk factors was found more often among men than women. Preventive actions which promote proper nutrition, more physical activity, smoking cessation and regular blood pressure checks and lipid profile tests should be implemented for the students.

Detection and characterization of atherosclerotic plaques by Raman probe spectroscopy and optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Matthäus, Christian; Dochow, Sebastian; Egodage, Kokila D.; Schie, Iwan; Romeike, Bernd F.; Brehm, Bernhard R.; Popp, Jürgen

2017-02-01

Visualization and characterization of inner arterial plaque depositions is of vital diagnostic interest. Established intravascular imaging techniques provide valuable morphological information, but cannot deliver information about the chemical composition of individual plaques. Probe based Raman spectroscopy offers the possibility for a biochemical characterization of atherosclerotic plaque formations during an intravascular intervention. From post mortem studies it is well known that the severity of a plaque and its stability are strongly correlated with its biochemical composition. Especially the identification of vulnerable plaques remains one of the most important and challenging aspects in cardiology. Thus, specific information about the composition of a plaque would greatly improve the risk assessment and management. Furthermore, knowledge about the composition can offer new therapeutic and medication strategies. Plaque calcifications as well as major lipid components such as cholesterol, cholesterol esters and triglycerides can be spectroscopically easily differentiated. Intravascular optical coherence tomography (OCT) is currently a prominent catheter based imaging technique for the localization and visualization of atherosclerotic plaque depositions. The high resolution of OCT with 10 to 15 µm allows for very detailed characterization of morphological features such as different plaque formations, thin fibrous caps and accurate measurements of lesion lengths. In combination with OCT imaging the obtained spectral information can provide substantial information supporting on on-site diagnosis of various plaque types and therefor an improved risk assessment. The potential and feasibility of combining OCT with Raman spectroscopy is demonstrated on excised plaque samples, as well as under in vivo conditions. Acknowledgements: Financial support from the Carl Zeiss Foundation is greatly acknowledged.

Ex-vivo UV autofluorescence imaging and fluorescence spectroscopy of atherosclerotic pathology in human aorta

NASA Astrophysics Data System (ADS)

Lewis, William; Williams, Maura; Franco, Walfre

2017-02-01

The aim of our study was to identify fluorescence excitation-emission pairs correlated with atherosclerotic pathology in ex-vivo human aorta. Wide-field images of atherosclerotic human aorta were captured using UV and visible excitation and emission wavelength pairs of several known fluorophores to investigate correspondence with gross pathologic features. Fluorescence spectroscopy and histology were performed on 21 aortic samples. A matrix of Pearson correlation coefficients were determined for the relationship between relevant histologic features and the intensity of emission for 427 wavelength pairs. A multiple linear regression analysis indicated that elastin (370/460 nm) and tryptophan (290/340 nm) fluorescence predicted 58% of the variance in intima thickness (R-squared = 0.588, F(2,18) = 12.8, p=.0003), and 48% of the variance in media thickness (R-squared = 0.483, F(2,18) = 8.42, p=.002), suggesting that endogenous fluorescence intensity at these wavelengths can be utilized for improved pathologic characterization of atherosclerotic plaques.

Immunochemical detection of food-derived polyphenols in the aorta: macrophages as a major target underlying the anti-atherosclerotic activity of polyphenols.

PubMed

Kawai, Yoshichika

2011-01-01

It has been suggested that polyphenol-rich diets decrease the risk of cardiovascular diseases. Although studies of the bioavailability of polyphenols, particularly their absorption and metabolism, have been reported recently, the tissue and cellular distributions underlying their biological mechanisms remain unknown. It is difficult to evaluate the specific localization of tissue and/or cellular polyphenols, because the method is limited to chromatography. To overcome these difficulties, we have developed anti-polyphenol antibodies to characterize immunohistochemically the localization of polyphenols and their metabolites in vivo. Two novel monoclonal antibodies were raised against quercetin and tea catechins, which represent flavonoid-type polyphenols distributed in foods and beverages, and are expected to exhibit anti-oxidative and anti-inflammatory activities in vivo. Using these antibodies, we identified activated macrophages as a specific target of these flavonoids during the development of atherosclerotic lesions. This review describes recent findings on the molecular actions of flavonoids that underly their anti-atherosclerotic activity in vivo.

Atherosclerotic Disease in Type 2 Diabetes Is Associated With an Increase in Sclerostin Levels

PubMed Central

Morales-Santana, Sonia; García-Fontana, Beatriz; García-Martín, Antonia; Rozas-Moreno, Pedro; García-Salcedo, José Antonio; Reyes-García, Rebeca; Muñoz-Torres, Manuel

2013-01-01

OBJECTIVE Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years). RESULTS Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group (P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD (P = 0.04), abnormal intima-media thickness (IMT) (P = 0.004), carotid plaques (P < 0.001), and aortic calcification (P < 0.001). In females, higher levels of sclerostin were related to abnormal IMT (P = 0.03) and aortic calcifications (P = 0.004). Homocysteine (β = 0.319 [95% CI 0.561–2.586], P = 0.003) and IMT (β = 0.330 [14.237–67.693], P = 0.003) were positively correlated with sclerostin. CONCLUSIONS Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients. PMID:23288857

Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study.

PubMed

Kundel, Vaishnavi; Trivieri, Maria Giovanna; Karakatsanis, Nicolas A; Robson, Phillip M; Mani, Venkatesh; Kizer, Jorge R; Kaplan, Robert; Fayad, Zahi; Shah, Neomi

2018-03-05

Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging - hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer-before and after continuous positive airway pressure (CPAP). Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3-6 months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP. Five patients were recruited as part of a focused project. Mean age was 52 years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBR mean ) and 6.2% (TBR max ) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others). We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: a report from the Chronic Renal Insufficiency Cohort (CRIC) study.

PubMed

Dobre, Mirela; Yang, Wei; Chen, Jing; Drawz, Paul; Hamm, L Lee; Horwitz, Edward; Hostetter, Thomas; Jaar, Bernard; Lora, Claudia M; Nessel, Lisa; Ojo, Akinlolu; Scialla, Julia; Steigerwalt, Susan; Teal, Valerie; Wolf, Myles; Rahman, Mahboob

2013-10-01

The purpose of this study is to evaluate serum bicarbonate level as a risk factor for renal outcomes, cardiovascular events, and mortality in patients with chronic kidney disease (CKD). Observational cohort study. 3,939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and December 2008. Serum bicarbonate level. Renal outcomes, defined as end-stage renal disease (either initiation of dialysis therapy or kidney transplantation) or 50% reduction in estimated glomerular filtration rate (eGFR); atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease); congestive heart failure events; and death. Time to event. Mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m(2), and median serum bicarbonate level was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, 332 experienced an atherosclerotic event, and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal end point was 3% lower per 1-mEq/L increase in serum bicarbonate level (HR, 0.97; 95% CI, 0.94-0.99; P = 0.01). The association was stronger for participants with eGFR >45 mL/min/1.73 m(2) (HR, 0.91; 95% CI, 0.85-0.97; P = 0.004). The risk of heart failure increased by 14% (HR, 1.14; 95% CI, 1.03-1.26; P = 0.02) per 1-mEq/L increase in serum bicarbonate level over 24 mEq/L. Serum bicarbonate level was not associated independently with atherosclerotic events (HR, 0.99; 95% CI, 0.95-1.03; P = 0.6) and all-cause mortality (HR, 0.98; 95% CI, 0.95-1.02; P = 0.3). Single measurement of sodium bicarbonate. In a cohort of participants with CKD, low serum bicarbonate level was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate levels. There was no association between serum bicarbonate level and all

Association of Serum Bicarbonate With Risk of Renal and Cardiovascular Outcomes in CKD: A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study

PubMed Central

Dobre, Mirela; Yang, Wei; Chen, Jing; Drawz, Paul; Hamm, L. Lee; Horwitz, Edward; Hostetter, Thomas; Jaar, Bernard; Lora, Claudia M; Nessel, Lisa; Ojo, Akinlolu; Scialla, Julia; Steigerwalt, Susan; Teal, Valerie; Wolf, Myles; Rahman, Mahboob

2013-01-01

Background The purpose of this study is to evaluate serum bicarbonate as a risk factor for renal outcomes, cardiovascular events and mortality in patients with chronic kidney disease (CKD). Study Design Observational cohort study. Setting & Participants 3939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 - December 2008. Predictor Serum bicarbonate. Outcomes Renal outcomes, defined as end-stage renal disease (either initiation of dialysis or kidney transplantation) or 50% reduction in eGFR; atherosclerotic events (myocardial infarction, stroke, peripheral arterial disease); congestive heart failure events; and death. Measurements Time to event. Results The mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m2, and the median serum bicarbonate was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, and 332 experienced an atherosclerotic event and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal endpoint was 3% lower per mEq/L increase in serum bicarbonate (HR, 0.97; 95% CI, 0.94-0.99; p=0.01). The association was stronger for participants with eGFR> 45ml/min/1.73m2 (HR, 0.91; 95%CI, 0.85-0.97; p=0.004). The risk of heart failure increased by 14% (HR, 1.14; 95%CI, 1.03-1.26; p=0.02) per mEq/L increase in serum bicarbonate over 24 mEq/L. Serum bicarbonate was not independently associated with atherosclerotic events (HR, 0.99; 95%CI, 0.95-1.03; p=0.6) and all-cause mortality (HR, 0.98; 95%CI, 0.95-1.02; p=0.3). Limitations Single measurement of sodium bicarbonate. Conclusions In a cohort of participants with CKD, low serum bicarbonate was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate. There was no association between serum bicarbonate and all

Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques.

PubMed

Luo, Yuemei; Cui, Dongyao; Yu, Xiaojun; Chen, Si; Liu, Xinyu; Tang, Hongying; Wang, Xianghong; Liu, Linbo

2016-01-01

Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals.

Lactobacillus acidophilus ATCC 4356 attenuates the atherosclerotic progression through modulation of oxidative stress and inflammatory process.

PubMed

Chen, Lihua; Liu, Wenen; Li, Yanming; Luo, San; Liu, Qingxia; Zhong, Yiming; Jian, Zijuan; Bao, Meihua

2013-09-01

The aim of this study was to investigate the effect of Lactobacillus (L.) acidophilus ATCC 4356 on the progression of atherosclerosis in Apoliprotein-E knockout (ApoE(-/-)) mice and the underlying mechanisms. Eight week-old ApoE(-/-) mice were treated with L. acidophilus ATCC 4356 daily for 12 weeks. The wild type (WT) mice or ApoE(-/-) mice in the vehicle group were treated with saline only. Body weights, serum lipid levels, aortic atherosclerotic lesions, and tissue oxidative and inflammatory statuses were examined among the groups. As compared to ApoE(-/-) mice in the vehicle group, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 had no changes in body weights and serum lipid profiles, but showed decreased atherosclerotic lesion size in en face aorta. In comparison with WT mice, ApoE(-/-) mice in the vehicle group showed higher levels of serum malondialdehyde (MDA), oxidized low density lipoprotein (oxLDL) and tumor necrosis factor-alpha (TNF-α), but lower levels of interleukin-10 (IL-10) and superoxide dismutase (SOD) activities in serum. Administration of L. acidophilus ATCC 4356 could reverse these trends in a dose-dependent manner in ApoE(-/-) mice. Furthermore, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 showed an inhibition of translocation of NF-κB p65 from cytoplasm to nucleus, suppression of degradation of aortic IκB-α, and improvements of gut microbiota distribution, as compared to ApoE(-/-) mice in the vehicle group. Our findings suggest that administration of L. acidophilus ATCC 4356 can attenuate the development of atherosclerotic lesions in ApoE(-/-) mice through reducing oxidative stress and inflammatory response. Copyright © 2013 Elsevier B.V. All rights reserved.

Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk?

PubMed

Nelson, John R; True, Wayne S; Le, Viet; Mason, R Preston

2017-11-01

Residual cardiovascular (CV) risk persists even in statin-treated patients with optimized low-density lipoprotein cholesterol (LDL-C) levels. Other pathways beyond cholesterol contribute to CV risk and the key to reducing residual risk may be addressing non-cholesterol risk factors through pleiotropic mechanisms. The purpose of this review is to examine the literature relating to the potential role of the omega-3 fatty acid eicosapentaenoic acid (EPA) in reducing residual CV risk. The literature shows that EPA can robustly lower plasma triglyceride (TG) levels without raising LDL-C levels and documents EPA to have a broad range of beneficial effects on the atherosclerotic pathway, including those on lipids, lipoproteins, inflammation, oxidation, phospholipid membranes, and the atherosclerotic plaque itself. Clinical imaging studies have consistently demonstrated that EPA decreases plaque vulnerability and prevents plaque progression. The evidence therefore points to a potential role for EPA to reduce residual CV risk. A large randomized study of statin-treated Japanese patients demonstrated that EPA ethyl ester reduced major coronary events by 19% (P = 0.011). However, while there has been significant benefit demonstrated in this and another Japanese CV outcomes study, the question as to whether EPA can play a role in reducing residual CV risk remains to be addressed in broader populations. The large, global, ongoing, randomized, placebo-controlled REDUCE-IT study of high-risk statin-treated patients with persistent hypertriglyceridemia is currently underway to investigate the potential of icosapent ethyl (high-purity prescription EPA ethyl ester) as an add-on therapy to reduce residual CV risk.

An Improvement of Cardiovascular Risk Factors by Omega-3 Polyunsaturated Fatty Acids.

PubMed

Yanai, Hidekatsu; Masui, Yoshinori; Katsuyama, Hisayuki; Adachi, Hiroki; Kawaguchi, Akiko; Hakoshima, Mariko; Waragai, Yoko; Harigae, Tadanao; Sako, Akahito

2018-04-01

An epidemiological survey in the Northwest Greenland reported that the Greenlanders have a lower frequency of acute myocardial infarction and diabetes mellitus. The very low incidence of ischemic heart disease in the Greenlanders was explained by consumption of a diet rich in omega-3 polyunsaturated fatty acids (PUFAs). Possible anti-atherothrombotic effects of omega-3 PUFA include an improvement of lipid metabolism such as a reduction of triglyceride and an increase of high-density lipoprotein-cholesterol (HDL-C), and glucose metabolism, anti-platelet activity, anti-inflammatory effects, an improvement of endothelial function and stabilization of atherosclerotic plaque. The present study reviews an improvement of cardiovascular risk factors such as dyslipidemia and diabetes due to consumption of omega-3 PUFA. A sufficient number of studies suggest that omega-3 PUFA supplementation reduces serum triglyceride and increases HDL-cholesterol. The mechanisms for omega-3 PUFA-mediated improvements of lipid metabolism have been partially elucidated. The studies using experimental animals, part of trials in humans, have shown the beneficial effects of omega-3 PUFA on glucose metabolism and insulin sensitivity. The meta-analysis showed that omega-3 PUFA might prevent development of diabetes in part of population. Further studies should be performed to elucidate the association of omega-3 PUFA supplementation with diabetes, in the future.

Selective removal of cholesterol ester in atherosclerotic plaque using nanosecond pulsed laser at 5.75 μm

NASA Astrophysics Data System (ADS)

Ishii, K.; Tsukimoto, H.; Hazama, H.; Awazu, K.

2008-02-01

Laser angioplasty, for example XeCl excimer laser angioplasty, has gained more attention in addition to conventional methods of surgical and interventional treatment of atherosclerotic diseases such as bypass operation and balloon dilatation. Low degrees of thermal damage after ablation of atherosclerotic lesions have been achieved by XeCl excimer laser at 308 nm. However, in most cases, laser ablation is not selective and normal arterial wall is also damaged. To avoid complications such as severe dissections or perforation of the arterial wall in an angioplasty, a laser light source with high ablation efficiency but low arterial wall injury is desirable. At atherosclerotic lesions, cholesterol accumulates on the tunica intima by establishing an ester bond with fatty acids such as oleic acid, and thus cholesterol ester is the main component of atherosclerotic plaques. Mid-infrared pulsed laser at 5.75 μm is selectively well absorbed in C=O stretching vibration mode of ester bonds. The purpose of this study is to determine the effectiveness of nanosecond pulsed laser at 5.75 μm irradiation of cholesterol ester in atherosclerotic plaques. In this study, we used a mid-infrared tunable solid-state laser which is operated by difference frequency generation method, with a wavelength of 5.75 μm, a pulse width of 5 nsec and a pulse duration of 10 Hz. It was confirmed that non-invasive interaction to normal thoracic aortas could be induce by the parameters, the wavelength of 5.75 μm, the average power densities of 35 W/cm2 and the irradiation time under 10 sec. This study shows that nanosecond pulsed laser irradiations at 5.75 μm provide an alternative laser light source as an effectively cutting, less traumatic tool for removal of atherosclerotic plaque.

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques.

PubMed

Yatera, Kazuhiro; Hsieh, Joanne; Hogg, James C; Tranfield, Erin; Suzuki, Hisashi; Shih, Chih-Horng; Behzad, Ali R; Vincent, Renaud; van Eeden, Stephan F

2008-02-01

Epidemiologic studies have shown an association between exposure to ambient particulate air pollution <10 microm in diameter (PM(10)) and increased cardiovascular morbidity and mortality. We previously showed that PM(10) exposure causes progression of atherosclerosis in coronary arteries. We postulate that the recruitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM(10)-induced acceleration of atherosclerosis. The study objective was to quantify the recruitment of circulating monocytes into vessel walls and the progression of atherosclerotic plaques induced by exposure to PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo-2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM(10) caused progression of atherosclerotic lesions in thoracic and abdominal aorta. It also decreased circulating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platelet endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the number of BrdU-labeled monocytes adherent to endothelium over plaques and increased the migration of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conclude that exposure to ambient air pollution particles promotes the recruitment of circulating monocytes into atherosclerotic plaques and speculate that this is a critically important step in the PM(10)-induced progression of atherosclerosis.

Stable phase post-MI patients have elevated VEGF levels correlated with inflammation markers, but not with atherosclerotic burden.

PubMed

ErŽen, Barbara; Šilar, Mira; Šabovič, Mišo

2014-11-22

The role of vascular endothelial growth factor (VEGF) in patients in the stable phase after myocardial infarction (MI) has not yet been explored. Therefore, we compared the values of VEGF in post-MI patients with those obtained in healthy controls. Furthermore, we investigated whether the values of VEGF correlate to either inflammation markers or the atherosclerotic burden. 41 male patients (on average 44 years old) in the stable phase after MI (on average 20.5 months after MI) were recruited, while 25 healthy age-matched males served as controls. Plasma levels of VEGF and several markers of inflammation were measured by standard procedures. The atherosclerotic burden was determined by the angiographic severity of coronary atherosclerosis, endothelial dysfunction (measured by ultrasound measurement of the flow mediated dilation of the brachial artery), the intima-media thickness of the common carotid artery and the ankle-brachial pressure index. VEGF values were significantly elevated in post-MI patients compared to the controls (53.8 ± 42.7 pg/ml vs. 36.3 ± 8.9 pg/ml, p = 0.014). The elevated VEGF values significantly correlated to the (increased) values of the inflammatory molecules interleukin 6 and 8 (r = 0.37, p = 0.017; and r = 0.45, p = 0.003; respectively). In contrast, no correlation was found between VEGF and the parameters of the atherosclerotic burden, although FMD and IMT were significantly impaired in patients. We found that plasma levels of VEGF are increased in the stable phase after MI and correlate with inflammation cytokines, but not with the atherosclerotic burden. Thus, this suggests that increased levels of VEGF are a part of ongoing inflammatory activity. Since VEGF in these patients stimulates neovascularization of inflamed plaques and induces their destabilization, the VEGF level can have an important negative prognostic value. Clearly, further studies are needed to clarify the role of VEGF as a prognostic marker.

Periodontitis is an independent risk indicator for atherosclerotic cardiovascular diseases among 60 174 participants in a large dental school in the Netherlands

PubMed Central

Beukers, Nicky G F M; van der Heijden, Geert J M G; van Wijk, Arjen J; Loos, Bruno G

2017-01-01

Background The association between periodontitis and atherosclerotic cardiovascular diseases (ACVD) has been established in some modestly sized studies (<10 000). Rarely, however, periodontitis has been studied directly; often tooth loss or self-reported periodontitis has been used as a proxy measure for periodontitis. Our aim is to investigate the adjusted association between periodontitis and ACVD among all individuals registered in a large dental school in the Netherlands (Academic Centre for Dentistry Amsterdam (ACTA)). Methods Anonymised data were extracted from the electronic health records for all registered patients aged >35 years (period 1998–2013). A participant was recorded as having periodontitis based on diagnostic and treatment codes. Any affirmative answer for cerebrovascular accidents, angina pectoris and/or myocardial infarction labelled a participant as having ACVD. Other risk factors for ACVD, notably age, sex, smoking, diabetes, hypertension, hypercholesterolaemia and social economic status, were also extracted. Logistic regression analyses were used to evaluate the adjusted associations between periodontitis and ACVD. Results 60 174 individuals were identified; 4.7% of the periodontitis participants (455/9730) and 1.9% of the non-periodontitis participants (962/50 444) reported ACVD; periodontitis showed a significant association with ACVD (OR 2.52; 95% CI 2.3 to 2.8). After adjustment for the confounders, periodontitis remained independently associated with ACVD (OR 1.59; 95% CI 1.39 to 1.81). With subsequent stratification for age and sex, periodontitis remained independently associated with ACVD. Conclusions This cross-sectional analysis of a large cohort in the Netherlands of 60 174 participants shows the independent association of periodontitis with ACVD. PMID:27502782

Lifetime cardiovascular risk of childhood obesity.

PubMed

Raghuveer, Geetha

2010-05-01

An increase in the incidence and an earlier onset of coronary artery disease is expected because of the increased prevalence of childhood obesity. Comorbidities of obesity, such as dyslipidemia, insulin resistance syndrome, hypertension, associated nutritional deficiencies, and a sedentary lifestyle or associated lifestyle factors such as tobacco smoke exposure, are likely to account for this increase because these are all independent risk factors for accelerated atherosclerosis. Because clinical atherosclerotic cardiovascular disease does not manifest in obese children, assessment of the subclinical markers of atherosclerosis may help in the evaluation of the progression of atherosclerosis, in further stratification of risk, and in monitoring the effects of intervention. Furthermore, because multiple risk factors with poorly understood interplay might be present in obese children, assessment of the vasculature directly, and perhaps the assignment of a "vascular age," may be a useful method to quantify the "end organ" effect of exposure to these various risks. Obese children may show favorable changes in their behaviors that result in an improvement in clinically measurable risk factors with various clinic-based and behavior modification therapies, but the vascular benefits of such interventions need to be studied further. Broad social, cultural, legislative, and policy changes that support healthy lifestyles within families and communities need to be implemented to decrease the prevalence of childhood obesity and its cardiovascular consequences in communities. The effect of risk factor modification on the vasculature will continue to be a resource for the direction of evidence-based therapy in obese children.

Prognostic implications of surrogate markers of atherosclerosis in low to intermediate risk patients with Type 2 Diabetes

PubMed Central

2012-01-01

Background Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients. Methods We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10 years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61 ± 16 months. Results A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0 ± 4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59 ± 0.07 (P = 0.21). Among different vascular assessments, CACS > 40 had the best prognostic value (AUC 0.81 ± 0.06, P < 0.01) and offered significantly better accuracy in prediction compared with FRS (P = 0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS > 40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P = 0.002). Conclusions In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS > 40 was an independent predictor for atherosclerotic events. PMID:22900680

Precision phenotyping, panomics, and system-level bioinformatics to delineate complex biologies of atherosclerosis: rationale and design of the "Genetic Loci and the Burden of Atherosclerotic Lesions" study.

PubMed

Voros, Szilard; Maurovich-Horvat, Pal; Marvasty, Idean B; Bansal, Aruna T; Barnes, Michael R; Vazquez, Gustavo; Murray, Sarah S; Voros, Viktor; Merkely, Bela; Brown, Bradley O; Warnick, G Russell

2014-01-01

Complex biological networks of atherosclerosis are largely unknown. The main objective of the Genetic Loci and the Burden of Atherosclerotic Lesions study is to assemble comprehensive biological networks of atherosclerosis using advanced cardiovascular imaging for phenotyping, a panomic approach to identify underlying genomic, proteomic, metabolomic, and lipidomic underpinnings, analyzed by systems biology-driven bioinformatics. By design, this is a hypothesis-free unbiased discovery study collecting a large number of biologically related factors to examine biological associations between genomic, proteomic, metabolomic, lipidomic, and phenotypic factors of atherosclerosis. The Genetic Loci and the Burden of Atherosclerotic Lesions study (NCT01738828) is a prospective, multicenter, international observational study of atherosclerotic coronary artery disease. Approximately 7500 patients are enrolled and undergo non-contrast-enhanced coronary calcium scanning by CT for the detection and quantification of coronary artery calcium, as well as coronary artery CT angiography for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. In addition, patients undergo whole genome sequencing, DNA methylation, whole blood-based transcriptome sequencing, unbiased proteomics based on mass spectrometry, as well as metabolomics and lipidomics on a mass spectrometry platform. The study is analyzed in 3 subsequent phases, and each phase consists of a discovery cohort and an independent validation cohort. For the primary analysis, the primary phenotype will be the presence of any atherosclerotic plaque, as detected by cardiac CT. Additional phenotypic analyses will include per patient maximal luminal stenosis defined as 50% and 70% diameter stenosis. Single-omic and multi-omic associations will be examined for each phenotype; putative biomarkers will be assessed for association, calibration, discrimination, and reclassification. Copyright �

Identification of Atherosclerotic Plaques in Carotid Artery by Fluorescence Spectroscopy

NASA Astrophysics Data System (ADS)

Rocha, Rick; Villaverde, Antonio Balbin; Silveira, Landulfo; Costa, Maricília Silva; Alves, Leandro Procópio; Pasqualucci, Carlos Augusto; Brugnera, Aldo

2008-04-01

The aim of this work was to identify the presence of atherosclerotic plaques in carotid artery using the Fluorescence Spectroscopy. The most important pathogeny in the cardiovascular disorders is the atherosclerosis, which may affect even younger individuals. With approximately 1.2 million heart attacks and 750,000 strokes afflicting an aging American population each year, cardiovascular disease remains the number one cause of death. Carotid artery samples were obtained from the Autopsy Service at the University of São Paulo (São Paulo, SP, Brazil) taken from cadavers. After a histopathological analysis the 60 carotid artery samples were divided into two groups: normal (26) and atherosclerotic plaques (34). Samples were irradiated with the wavelength of 488 nm from an Argon laser. A 600 μm core optical fiber, coupled to the Argon laser, was used for excitation of the sample, whereas another 600 optical fiber, coupled to the spectrograph entrance slit, was used for collecting the fluorescence from the sample. Measurements were taken at different points on each sample and then averaged. Fluorescence spectra showed a single broad line centered at 549 nm. The fluorescence intensity for each sample was calculated by subtracting the intensity at the peak (550 nm) and at the bottom (510 nm) and then data were statistically analyzed, looking for differences between both groups of samples. ANOVA statistical test showed a significant difference (p<0,05) between both types of tissues, with regard to the fluorescence peak intensities. Our results indicate that this technique could be used to detect the presence of the atherosclerotic in carotid tissue.

A single-photon fluorescence and multi-photon spectroscopic study of atherosclerotic lesions

NASA Astrophysics Data System (ADS)

Smith, Michael S. D.; Ko, Alex C. T.; Ridsdale, Andrew; Schattka, Bernie; Pegoraro, Adrian; Hewko, Mark D.; Shiomi, Masashi; Stolow, Albert; Sowa, Michael G.

2009-06-01

In this study we compare the single-photon autofluorescence and multi-photon emission spectra obtained from the luminal surface of healthy segments of artery with segments where there are early atherosclerotic lesions. Arterial tissue was harvested from atherosclerosis-prone WHHL-MI rabbits (Watanabe heritable hyperlipidemic rabbit-myocardial infarction), an animal model which mimics spontaneous myocardial infarction in humans. Single photon fluorescence emission spectra of samples were acquired using a simple spectrofluorometer set-up with 400 nm excitation. Samples were also investigated using a home built multi-photon microscope based on a Ti:sapphire femto-second oscillator. The excitation wavelength was set at 800 nm with a ~100 femto-second pulse width. Epi-multi-photon spectroscopic signals were collected through a fibre-optics coupled spectrometer. While the single-photon fluorescence spectra of atherosclerotic lesions show minimal spectroscopic difference from those of healthy arterial tissue, the multi-photon spectra collected from atherosclerotic lesions show marked changes in the relative intensity of two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) signals when compared with those from healthy arterial tissue. The observed sharp increase of the relative SHG signal intensity in a plaque is in agreement with the known pathology of early lesions which have increased collagen content.

Stenting and medical therapy for atherosclerotic renal-artery stenosis.

PubMed

Cooper, Christopher J; Murphy, Timothy P; Cutlip, Donald E; Jamerson, Kenneth; Henrich, William; Reid, Diane M; Cohen, David J; Matsumoto, Alan H; Steffes, Michael; Jaff, Michael R; Prince, Martin R; Lewis, Eldrin F; Tuttle, Katherine R; Shapiro, Joseph I; Rundback, John H; Massaro, Joseph M; D'Agostino, Ralph B; Dworkin, Lance D

2014-01-02

Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03). Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).

SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice.

PubMed

Zheng, Lingyun; Wu, Teng; Zeng, Cuiling; Li, Xiangli; Li, Xiaoqiang; Wen, Dingwen; Ji, Tianxing; Lan, Tian; Xing, Liying; Li, Jiangchao; He, Xiaodong; Wang, Lijing

2016-01-01

Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression. we generated apoE(-/-); SAP(-/-) (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development. SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE(-/-) mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE(-/-) mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages. SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE(-/-) mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Risk factors in school shootings.

PubMed

Verlinden, S; Hersen, M; Thomas, J

2000-01-01

Nine incidents of multiple-victim homicide in American secondary schools are examined and common risk factors are identified. The literature dealing with individual, family, social, societal, and situational risk factors for youth violence and aggression is reviewed along with existing risk assessment methods. Checklists of risk factors for serious youth violence and school violence are used in reviewing each school shooting case. Commonalties among the cases and implications for psychologists practicing in clinical and school settings are discussed.

Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo

PubMed Central

Yang, Jing-Jing; Li, Peng; Wang, Fu; Liang, Wen-Jing; Ma, Hui; Chen, Yuan; Ma, Zhi-Min; Li, Quan-Zhong; Peng, Qi-Sheng; Zhang, Yun; Wang, Shuang-Xi

2016-01-01

Aims Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. Methods and Results In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2α phosphorylation and its activity, upregulated IkBα mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects. Conclusion Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis. PMID:27391154

Cardiovascular risk factors among college students: Knowledge, perception, and risk assessment.

PubMed

Tran, Dieu-My T; Zimmerman, Lani M; Kupzyk, Kevin A; Shurmur, Scott W; Pullen, Carol H; Yates, Bernice C

2017-04-01

To assess college students' knowledge and perception of cardiovascular risk factors and to screen for their cardiovascular risks. The final sample that responded to recruitment consisted of 158 college students from a midwestern university. A cross-sectional, descriptive study was performed using convenience sampling. College students were knowledgeable about cardiovascular risk factors but did not perceive themselves at risk for cardiovascular disease (CVD). Knowledge of cardiovascular risk factors was correlated with the lifetime risk estimates (ρ = .17, p = .048), and perception of cardiovascular risk was positively associated with 30-year CVD risk estimates (ρ = .16, p = .048). More than 50% of the participants had 1 or more cardiovascular risk factors. High knowledge level of cardiovascular risk factors was not sufficient to lower cardiovascular risks within this study population, but changing perception of cardiovascular risk factors may play a bigger role in reducing long-term cardiovascular risks.

Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability.

PubMed

Veiner, Hilla-Lee; Gorbatov, Rostic; Vardi, Moshe; Doros, Gheorghe; Miller-Lotan, Rachel; Zohar, Yaniv; Sabo, Edmond; Asleh, Rabea; Levy, Nina S; Goldfarb, Levi J; Berk, Thomas A; Haas, Tali; Shalom, Hadar; Suss-Toby, Edith; Kam, Adi; Kaplan, Marielle; Tamir, Ronit; Ziskind, Anna; Levy, Andrew P

2015-03-01

Homozygosity for a 1.7 kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2-3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE(-/-) background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Innate inflammation as the common pathway of risk factors leading to TIAs and stroke.

PubMed

del Zoppo, Gregory J; Gorelick, Philip B

2010-10-01

In the early moments of ischemic stroke, the processes of thrombosis, ischemia, and inflammation are intimately interrelated, setting in motion an injury that leads to infarction and permanent damage. Of these, the potential roles that innate inflammation can play in the evolution of brain tissue damage in response to the ischemic injury are not well understood. Observations in the settings of atherosclerotic cardiovascular disease and cerebral ischemia have much to teach each other. The following provides an introductory overview of the conference "Innate Inflammation as the Common Pathway of Risk Factors Leading to Transient Ischemic Attacks and Stroke: Pathophysiology and Potential Interventions," which took place May 9-10, 2010 at the New York Academy of Sciences. This meeting was convened to explore aspects of the cellular and tissue responses to innate inflammation. A faculty of leading experts was assembled to discuss the role of inflammation in laboratory models of stroke and myocardial infarction, define possible novel means from laboratory evidence to alleviate or prevent inflammation underlying stroke and cardiovascular disease, and present information on current examples of clinical translation of these understandings in relation to human stroke and myocardial infarction. © 2010 New York Academy of Sciences.

Comparison of Gadofluorine-M and Gd-DTPA for Non-Invasive Staging of Atherosclerotic Plaque Stability Using MRI

PubMed Central

Ronald, John A.; Chen, Yuanxin; Belisle, Andre J.-L.; Hamilton, Amanda M.; Rogers, Kem A.; Hegele, Robert A.; Misselwitz, Bernd; Rutt, Brian K.

2009-01-01

Background Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. Here we determined the utility of the MR contrast agent Gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA. Methods and Results 5 control and 7 atherosclerotic rabbits were sequentially imaged following administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T1-weighted pulse sequence on a 3T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values following GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours post-injection, but not Gd-DTPA at peak enhancement, was shown to correlate with a quantitative histological morphology index related to these two plaque features. Conclusions GdF-enhanced MRI of atherosclerotic plaques allows non-invasive quantitative information about plaque composition to be acquired at multiple time points post-injection (within 1 and up to 24 hours post-injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events. PMID:19808597

Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE(-/-) mice.

PubMed

Knutsson, Anki; Hsiung, Sabrina; Celik, Selvi; Rattik, Sara; Mattisson, Ingrid Yao; Wigren, Maria; Scher, Howard I; Nilsson, Jan; Hultgårdh-Nilsson, Anna

2016-05-18

Androgen-deprivation therapy (ADT) for prostate cancer has been associated with increased risk for development of cardiovascular events and recent pooled analyses of randomized intervention trials suggest that this primarily is the case for patients with pre-existing cardiovascular disease treated with gonadotropin-releasing hormone receptor (GnRH-R) agonists. In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice. A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery. After 4 weeks of ADT, increased areas of necrosis was observed in stable plaques from leuprolide-treated mice (median and IQR plaque necrotic area in control, degarelix and leuprolide-treated mice were 0.6% (IQR 0-3.1), 0.2% (IQR 0-4.4) and 11.0% (IQR 1.0-19.8), respectively). There was also evidence of increased inflammation as assessed by macrophage immunohistochemistry in the plaques from leuprolide-treated mice, but we found no evidence of such changes in plaques from control mice or mice treated with degarelix. Necrosis destabilizes plaques and increases the risk for rupture and development of acute cardiovascular events. Destabilization of pre-existing atherosclerotic plaques could explain the increased cardiovascular risk in prostate cancer patients treated with GnRH-R agonists.

Is diabetes mellitus a risk factor for venous thromboembolism? A systematic review and meta-analysis of case-control and cohort studies.

PubMed

Gariani, Karim; Mavrakanas, Thomas; Combescure, Christophe; Perrier, Arnaud; Marti, Christophe

2016-03-01

Diabetes mellitus is a well-established risk factor for atherosclerotic disease, but its role in the occurrence of venous thromboembolism (VTE) has not been elucidated. We conducted a meta-analysis of published cohort and case-control studies to assess whether diabetes mellitus is a risk factor for VTE. We systematically searched MEDLINE and EMBASE for case-control and prospective cohort studies assessing association between the risk of venous thromboembolism and diabetes. Odds ratios (OR) from case-control studies were combined while for prospective studies hazard ratios (HR) were combined. Models with random effects were used. Meta-analyses were conducted separately for raw and adjusted measures of association. 24 studies were identified including 10 cohort studies (274,501 patients) and 14 case-control studies (1,157,086 patients). Meta-analysis of the prospective cohort studies demonstrated a significant association between diabetes and VTE (HR 1.60; 95% CI 1.35 to 1.89). This association was no longer present after analysis of multi-adjusted HRs (HR 1.10; 95% CI 0.77 to 1.56). Meta-analysis of case-control studies showed a significant association between diabetes and VTE (OR 1.57; 95%CI 1.17 to 2.12), but this association was no longer present when adjusted ORs were used (OR 1.18; 95%CI 0.89 to 1.56). The increased risk of VTE associated with diabetes mainly results from confounders rather than an intrinsic effect of diabetes on venous thrombotic risk. Therefore, no specific recommendations should apply for the management of diabetic patients at risk for VTE. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

The Clinical Significance of Separate Measurements of Carotid Arterial Wall to Assess the Risk Factor for Atherosclerosis.

PubMed

Kim, Ji-Hoon; Youn, Ho-Joong; Kim, Gee-Hee; Moon, Keon-Woong; Yoo, Ki-Dong; Kim, Chul-Min

2016-03-01

Carotid intima-media thickness (CIMT) is associated with several risk factors for atherosclerosis and has been consistently linked to cardiovascular and cerebrovascular disease. The clinical significance of separate measurements of CIMT, which is the sum of the intima (IT) and media thickness (MT), to use as an assessment of risk for atherosclerosis has not yet been fully established. Among 3377 patients who underwent B-mode ultrasound of carotid arteries and coronary angiography in the Medical Department of St. Mary's Hospital from September 2003 to March 2009, 1146 subjects (M:F = 616:530; mean age, 57.7 ± 12.1 years) who were diagnosed with normal coronary arteries were enrolled in this study. IT, MT, and CIMT of the enrolled patients were manually measured using high-frequency ultrasonography (15 MHz linear array transducer). In multivariate logistic regression analysis, age (β = 0.063, p < 0.0001), body mass index (BMI) (β = 0.028, p = 0.018), and hypertension (HTN) (β = 0.046, p = 0.0002) were associated with MT (R(2) = 0.256) and the IT/MT ratio (R(2) = 0.209). Age (β = 0.065, p < 0.0001), BMI (β = 0.025, p = 0.038), hemoglobin A1c (β = 0.045, p = 0.045), and HTN (β = 0.043, p = 0.0006) correlated with mean CIMT (R(2) = 0.230). Age (β = -0.071, p < 0.0001) and BMI (β = -0.046, p = 0.002) were associated with the IT/MT ratio (R(2) = 0.219) on the left side. Age (β = 0.093, p < 0.0001) was related to MT (R(2) = 0.265) and mean CIMT (R(2) = 0.243) on the left side. We noted different atherosclerotic risk factors were related to measurements of the arterial wall in different ways. Therefore, separate measurements of CIMT might be a useful method to assess the risk for atherosclerosis.

Association between diabetes and different components of coronary atherosclerotic plaque burden as measured by coronary multidetector computed tomography.

PubMed

Yun, Chun-Ho; Schlett, Christopher L; Rogers, Ian S; Truong, Quynh A; Toepker, Michael; Donnelly, Patrick; Brady, Thomas J; Hoffmann, Udo; Bamberg, Fabian

2009-08-01

The aim of the study was to assess differences in the presence, extent, and composition of coronary atherosclerotic plaque burden as detected by coronary multidetector computed tomography (MDCT) between patients with and without diabetes mellitus. We compared coronary atherosclerotic plaques (any plaque, calcified [CAP], non-calcified [NCAP, and mixed plaque [MCAP

Endovascular revascularization for aortoiliac atherosclerotic disease

PubMed Central

Aggarwal, Vikas; Waldo, Stephen W; Armstrong, Ehrin J

2016-01-01

Atherosclerotic iliac artery disease is increasingly being treated with endovascular techniques. A number of new stent technologies can be utilized with high long-term patency, including self-expanding stents, balloon-expandable stents, and covered stents, but comparative data on these stent types and in more complex lesions are lacking. This article provides a review of currently available iliac stent technologies, as well as complex procedural aspects of iliac artery interventions, including approaches to the treatment of iliac bifurcation disease, long segment occlusions, choice of stent type, and treatment of iliac artery in-stent restenosis. PMID:27099509

Ex vivo detection of macrophages in atherosclerotic plaques using intravascular ultrasonic-photoacoustic imaging

NASA Astrophysics Data System (ADS)

Quang Bui, Nhat; Hlaing, Kyu Kyu; Lee, Yong Wook; Kang, Hyun Wook; Oh, Junghwan

2017-01-01

Macrophages are excellent imaging targets for detecting atherosclerotic plaques as they are involved in all the developmental stages of atherosclerosis. However, no imaging technique is currently capable of visualizing macrophages inside blood vessel walls. The current study develops an intravascular ultrasonic-photoacoustic (IVUP) imaging system combined with indocyanine green (ICG) as a contrast agent to provide morphological and compositional information about the targeted samples. Both tissue-mimicking vessel phantoms and atherosclerotic plaque-mimicking porcine arterial tissues are used to demonstrate the feasibility of mapping macrophages labeled with ICG by endoscopically applying the proposed hybrid technique. A delay pulse triggering technique is able to sequentially acquire photoacoustic (PA) and ultrasound (US) signals from a single scan without using any external devices. The acquired PA and US signals are used to reconstruct 2D cross-sectional and 3D volumetric images of the entire tissue with the ICG-loaded macrophages injected. Due to high imaging contrast and sensitivity, the IVUP imaging vividly reveals structural information and detects the spatial distribution of the ICG-labeled macrophages inside the samples. ICG-assisted IVUP imaging can be a feasible imaging modality for the endoscopic detection of atherosclerotic plaques.

Stroke Risk Factors and Symptoms

MedlinePlus

... » [ pdf, 433 kb ] Order Materials » Stroke Risk Factors and Symptoms Risk Factors for a Stroke Stroke prevention is still ... it. Treatment can delay complications that increase the risk of stroke. Transient ischemic attacks (TIAs). Seek help. ...

Treatment of multiple-risk patients: using combination therapy to treat beyond LDL lowering.

PubMed

Weintraub, Howard S

2005-08-01

During the past 25 years, the role of traditional "risk factors" in the genesis of atherosclerotic vascular disease has been convincingly validated. The impact of elevated low-density lipoprotein cholesterol, hypertension, type II diabetes, and metabolic syndrome are now well accepted. However, until recently, there was guilt by association without a clear understanding of the manner in which the crime was committed. It is now acknowledged that the presence of multiple risk factors can increase the likelihood of an ischemic event. This has become a great concern, given the very high prevalence of patients who fall into this category. In light of this information, the mandate for appropriate guideline-driven therapy has become even stronger, and we must consider the use of multiple medications to effectively neutralize this risk.

Seismic Risk Perception compared with seismic Risk Factors

NASA Astrophysics Data System (ADS)

Crescimbene, Massimo; La Longa, Federica; Pessina, Vera; Pino, Nicola Alessandro; Peruzza, Laura

2016-04-01

The communication of natural hazards and their consequences is one of the more relevant ethical issues faced by scientists. In the last years, social studies have provided evidence that risk communication is strongly influenced by the risk perception of people. In order to develop effective information and risk communication strategies, the perception of risks and the influencing factors should be known. A theory that offers an integrative approach to understanding and explaining risk perception is still missing. To explain risk perception, it is necessary to consider several perspectives: social, psychological and cultural perspectives and their interactions. This paper presents the results of the CATI survey on seismic risk perception in Italy, conducted by INGV researchers on funding by the DPC. We built a questionnaire to assess seismic risk perception, with a particular attention to compare hazard, vulnerability and exposure perception with the real data of the same factors. The Seismic Risk Perception Questionnaire (SRP-Q) is designed by semantic differential method, using opposite terms on a Likert scale to seven points. The questionnaire allows to obtain the scores of five risk indicators: Hazard, Exposure, Vulnerability, People and Community, Earthquake Phenomenon. The questionnaire was administered by telephone interview (C.A.T.I.) on a statistical sample at national level of over 4,000 people, in the period January -February 2015. Results show that risk perception seems be underestimated for all indicators considered. In particular scores of seismic Vulnerability factor are extremely low compared with house information data of the respondents. Other data collected by the questionnaire regard Earthquake information level, Sources of information, Earthquake occurrence with respect to other natural hazards, participation at risk reduction activities and level of involvement. Research on risk perception aims to aid risk analysis and policy-making by

What We Have Learned from the Recent Meta-analyses on Diagnostic Methods for Atherosclerotic Plaque Regression.

PubMed

Biondi-Zoccai, Giuseppe; Mastrangeli, Simona; Romagnoli, Enrico; Peruzzi, Mariangela; Frati, Giacomo; Roever, Leonardo; Giordano, Arturo

2018-01-17

Atherosclerosis has major morbidity and mortality implications globally. While it has often been considered an irreversible degenerative process, recent evidence provides compelling proof that atherosclerosis can be reversed. Plaque regression is however difficult to appraise and quantify, with competing diagnostic methods available. Given the potential of evidence synthesis to provide clinical guidance, we aimed to review recent meta-analyses on diagnostic methods for atherosclerotic plaque regression. We identified 8 meta-analyses published between 2015 and 2017, including 79 studies and 14,442 patients, followed for a median of 12 months. They reported on atherosclerotic plaque regression appraised with carotid duplex ultrasound, coronary computed tomography, carotid magnetic resonance, coronary intravascular ultrasound, and coronary optical coherence tomography. Overall, all meta-analyses showed significant atherosclerotic plaque regression with lipid-lowering therapy, with the most notable effects on echogenicity, lipid-rich necrotic core volume, wall/plaque volume, dense calcium volume, and fibrous cap thickness. Significant interactions were found with concomitant changes in low density lipoprotein cholesterol, high density lipoprotein cholesterol, and C-reactive protein levels, and with ethnicity. Atherosclerotic plaque regression and conversion to a stable phenotype is possible with intensive medical therapy and can be demonstrated in patients using a variety of non-invasive and invasive imaging modalities.

Spatio-temporal texture (SpTeT) for distinguishing vulnerable from stable atherosclerotic plaque on dynamic contrast enhancement (DCE) MRI in a rabbit model

PubMed Central

Wan, Tao; Madabhushi, Anant; Phinikaridou, Alkystis; Hamilton, James A.; Hua, Ning; Pham, Tuan; Danagoulian, Jovanna; Kleiman, Ross; Buckler, Andrew J.

2014-01-01

Purpose: To develop a new spatio-temporal texture (SpTeT) based method for distinguishing vulnerable versus stable atherosclerotic plaques on DCE-MRI using a rabbit model of atherothrombosis. Methods: Aortic atherosclerosis was induced in 20 New Zealand White rabbits by cholesterol diet and endothelial denudation. MRI was performed before (pretrigger) and after (posttrigger) inducing plaque disruption with Russell's-viper-venom and histamine. Of the 30 vascular targets (segments) under histology analysis, 16 contained thrombus (vulnerable) and 14 did not (stable). A total of 352 voxel-wise computerized SpTeT features, including 192 Gabor, 36 Kirsch, 12 Sobel, 52 Haralick, and 60 first-order textural features, were extracted on DCE-MRI to capture subtle texture changes in the plaques over the course of contrast uptake. Different combinations of SpTeT feature sets, in which the features were ranked by a minimum-redundancy-maximum-relevance feature selection technique, were evaluated via a random forest classifier. A 500 iterative 2-fold cross validation was performed for discriminating the vulnerable atherosclerotic plaque and stable atherosclerotic plaque on per voxel basis. Four quantitative metrics were utilized to measure the classification results in separating between vulnerable and stable plaques. Results: The quantitative results show that the combination of five classes of SpTeT features can distinguish between vulnerable (disrupted plaques with an overlying thrombus) and stable plaques with the best AUC values of 0.9631 ± 0.0088, accuracy of 89.98% ± 0.57%, sensitivity of 83.71% ± 1.71%, and specificity of 94.55% ± 0.48%. Conclusions: Vulnerable and stable plaque can be distinguished by SpTeT based features. The SpTeT features, following validation on larger datasets, could be established as effective and reliable imaging biomarkers for noninvasively assessing atherosclerotic risk. PMID:24694153

Cardiovascular risk prediction in HIV-infected patients: comparing the Framingham, atherosclerotic cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models.

PubMed

Krikke, M; Hoogeveen, R C; Hoepelman, A I M; Visseren, F L J; Arends, J E

2016-04-01

The aim of the study was to compare the predictions of five popular cardiovascular disease (CVD) risk prediction models, namely the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, the Framingham Heart Study (FHS) coronary heart disease (FHS-CHD) and general CVD (FHS-CVD) models, the American Heart Association (AHA) atherosclerotic cardiovascular disease risk score (ASCVD) model and the Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) model. A cross-sectional design was used to compare the cumulative CVD risk predictions of the models. Furthermore, the predictions of the general CVD models were compared with those of the HIV-specific D:A:D model using three categories (< 10%, 10-20% and > 20%) to categorize the risk and to determine the degree to which patients were categorized similarly or in a higher/lower category. A total of 997 HIV-infected patients were included in the study: 81% were male and they had a median age of 46 [interquartile range (IQR) 40-52] years, a known duration of HIV infection of 6.8 (IQR 3.7-10.9) years, and a median time on ART of 6.4 (IQR 3.0-11.5) years. The D:A:D, ASCVD and SCORE-NL models gave a lower cumulative CVD risk, compared with that of the FHS-CVD and FHS-CHD models. Comparing the general CVD models with the D:A:D model, the FHS-CVD and FHS-CHD models only classified 65% and 79% of patients, respectively, in the same category as did the D:A:D model. However, for the ASCVD and SCORE-NL models, this percentage was 89% and 87%, respectively. Furthermore, FHS-CVD and FHS-CHD attributed a higher CVD risk to 33% and 16% of patients, respectively, while this percentage was < 6% for ASCVD and SCORE-NL. When using FHS-CVD and FHS-CHD, a higher overall CVD risk was attributed to the HIV-infected patients than when using the D:A:D, ASCVD and SCORE-NL models. This could have consequences regarding overtreatment, drug-related adverse events and drug-drug interactions. © 2015 British HIV Association.

Visualization of Monocytic Cells in Regressing Atherosclerotic Plaques by Intravital 2-Photon and Positron Emission Tomography-Based Imaging-Brief Report.

PubMed

Li, Wenjun; Luehmann, Hannah P; Hsiao, Hsi-Min; Tanaka, Satona; Higashikubo, Ryuji; Gauthier, Jason M; Sultan, Deborah; Lavine, Kory J; Brody, Steven L; Gelman, Andrew E; Gropler, Robert J; Liu, Yongjian; Kreisel, Daniel

2018-05-01

Aortic arch transplants have advanced our understanding of processes that contribute to progression and regression of atherosclerotic plaques. To characterize the dynamic behavior of monocytes and macrophages in atherosclerotic plaques over time, we developed a new model of cervical aortic arch transplantation in mice that is amenable to intravital imaging. Vascularized aortic arch grafts were transplanted heterotropically to the right carotid arteries of recipient mice using microsurgical suture techniques. To image immune cells in atherosclerotic lesions during regression, plaque-bearing aortic arch grafts from B6 ApoE-deficient donors were transplanted into syngeneic CX 3 CR1 GFP reporter mice. Grafts were evaluated histologically, and monocytic cells in atherosclerotic plaques in ApoE-deficient grafts were imaged intravitally by 2-photon microscopy in serial fashion. In complementary experiments, CCR2 + cells in plaques were serially imaged by positron emission tomography using specific molecular probes. Plaques in ApoE-deficient grafts underwent regression after transplantation into normolipidemic hosts. Intravital imaging revealed clusters of largely immotile CX 3 CR1 + monocytes/macrophages in regressing plaques that had been recruited from the periphery. We observed a progressive decrease in CX 3 CR1 + monocytic cells in regressing plaques and a decrease in CCR2 + positron emission tomography signal during 4 months. Cervical transplantation of atherosclerotic mouse aortic arches represents a novel experimental tool to investigate cellular mechanisms that contribute to the remodeling of atherosclerotic plaques. © 2018 American Heart Association, Inc.

Moderate overweight is beneficial and severe obesity detrimental for patients with documented atherosclerotic heart disease.

PubMed

Azimi, Aziza; Charlot, Mette Gitz; Torp-Pedersen, Christian; Gislason, Gunnar H; Køber, Lars; Jensen, Lisette Okkels; Thayssen, Per; Ravkilde, Jan; Tilsted, Hans-Henrik; Lassen, Jens Flensted; Thuesen, Leif

2013-05-01

Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease. This retrospective registry based cohort study included all patients from the Western Denmark Heart Registry with coronary atherosclerosis confirmed by coronary angiography from January 2000 to December 2010. Patients were divided into eight groups according to body mass index (BMI) based on WHO BMI classification. Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark. The study included 37 573 patients (70.7% men) with a mean age of (66.3 ± 11.1) years. During the 11 years of follow-up, 5866 (15.6%) patients died. Multivariable analysis confirmed that the risk of death was the lowest among the preobese patients (27.5 ≤ BMI<30 kg/m(2)) with adjusted HR of 0.82 (95% CI 0.71 to 0.95; p=0.008) and increased with both low (BMI<18.50 kg/m(2)) and very high (BMI ≥ 40 kg/m(2)) BMI, HR 2.04 (95% CI 1.63 to 2.57; p<0.001) and HR 1.35 (95% CI 1.05 to 1.72; p<0.01), respectively. Also the normal weight class I (18.5 ≤ BMI<23 kg/m(2)) had a significant risk of mortality HR 1.28 (95% CI 1.13 to 1.45; p<0.001). Obese classes I and II did not differ from the reference group (23 ≤ BMI<25 kg/m(2)). Overweight atherosclerotic heart disease patients have improved survival compared with normal weight patients. Underweight and severely obese patients have increased mortality. Our results lean more towards an overweight paradox than an obesity paradox.

Proteoglycan 4 regulates macrophage function without altering atherosclerotic lesion formation in a murine bone marrow-specific deletion model.

PubMed

Nahon, Joya E; Hoekstra, Menno; Havik, Stefan R; Van Santbrink, Peter J; Dallinga-Thie, Geesje M; Kuivenhoven, Jan-Albert; Geerling, Janine J; Van Eck, Miranda

2018-05-05

Proteoglycan 4 (Prg4) has a high structural similarity with the established atherosclerosis-modulating proteoglycan versican, but its role in atherogenesis is still unknown. Therefore, the impact of Prg4 deficiency on macrophage function in vitro and atherosclerosis susceptibility in vivo was investigated. The presence and localization of Prg4 was studied in atherosclerotic lesions. Furthermore, the effect of Prg4 deficiency on macrophage foam cell formation, cholesterol efflux and lipopolysaccharide (LPS) response was determined. Finally, susceptibility for atherosclerotic lesion formation was investigated in bone marrow-specific Prg4 knockout (KO) mice. Prg4 mRNA expression was induced 91-fold (p<0.001) in murine initial atherosclerotic lesions and Prg4 protein co-localized with human lesional macrophages. Murine Prg4 KO macrophages showed increased foam cell formation (+2.1-fold, p<0.01). In parallel, the expression of the cholesterol efflux genes ATP-binding cassette transporter A1 and scavenger receptor type B1 was lower (-35%, p<0.05;-40%, p<0.05) in Prg4 KO macrophages. This translated into an impaired cholesterol efflux to high-density lipoprotein (-13%, p<0.001) and apolipoprotein A1 (-8%, p<0.05). Furthermore, Prg4 KO macrophages showed an impaired LPS-induced rise in TNFα secretion as compared to wild-type controls (-31%, p<0.001), indicating a reduced inflammatory response. Combined, these pro- and anti-atherogenic effects did not translate into a significant difference in atherosclerotic lesion formation upon bone marrow-specific deletion of Prg4 in low-density lipoprotein receptor KO mice. Prg4 is present in macrophages in both murine and human atherosclerotic lesions and critically influences macrophage function, but deletion of Prg4 in bone marrow-derived cells does not affect atherosclerotic lesion development. Copyright © 2018 Elsevier B.V. All rights reserved.

Atorvastatin Upregulates the Expression of miR-126 in Apolipoprotein E-knockout Mice with Carotid Atherosclerotic Plaque.

PubMed

Pan, Xudong; Hou, Rongyao; Ma, Aijun; Wang, Ting; Wu, Mei; Zhu, Xiaoyan; Yang, Shaonan; Xiao, Xing

2017-01-01

Carotid atherosclerosis (AS) is a chronic inflammatory disease of the carotid arterial wall, which is very important in terms of the occurrence of cerebral vascular accidents. Studies have demonstrated that microRNAs (miRNAs) and their target genes are involved in the formation of atherosclerosis and that atorvastatin might reduce atherosclerotic plaques by regulating the expression of miRNAs. However, the related mechanism is not yet known. In this study, we first investigated the effects of atorvastatin on miR-126 and its target gene, i.e., vascular cell adhesion molecule-1 (VCAM-1) in apolipoprotein E-knockout (ApoE-/-) mice with carotid atherosclerotic plaque in vivo. We compared the expressions of miR-126 and VCAM-1 between the control, atherosclerotic model and atorvastatin treatment groups of ApoE-/- mice using RT-PCR and Western blot. We found the miR-126 expression was significantly down-regulated, and the VCAM-1 expression was significantly up-regulated in the atherosclerotic model group, which accelerated the progression of atherosclerosis in the ApoE-/- mice. These results following atorvastatin treatment indicated that miR-126 expression was significantly up-regulated, VCAM-1 expression was significantly down-regulated and atherosclerotic lesions were reduced. The present results might explain the mechanism by which miR-126 is involved in the formation of atherosclerosis in vivo. Our study first indicated that atorvastatin might exert its anti-inflammatory effects in atherosclerosis by regulating the expressions of miR-126 and VCAM-1 in vivo.

Synthesizing Risk from Summary Evidence Across Multiple Risk Factors.

PubMed

Shrier, Ian; Colditz, Graham A; Steele, Russell J

2018-07-01

Although meta-analyses provide summary effect estimates that help advise patient care, patients often want to compare their overall health to the general population. The Harvard Cancer Risk Index was published in 2004 and uses risk ratio estimates and prevalence estimates from original studies across many risk factors to provide an answer to this question. However, the published version of the formula only uses dichotomous risk factors and its derivation was not provided. The objective of this brief report was to provide the derivation of a more general form of the equation that allows the incorporation of risk factors with three or more levels.

Atherosclerotic changes of vessels caused by restriction of movement

NASA Technical Reports Server (NTRS)

Gvishiani, G. S.; Kobakhidze, N. G.; Mchedlishvili, M. G.; Dekanosidze, T. I.

1980-01-01

The effect of restriction of movement on the development of atheroscelerosis was studied in rabbits. Drastic restriction of movement for 20 and 30 days causes atherosclerotic alterations of the aorta and shifts in ECG which are characteristic of coronary atherosclerosis. At the same time, shortening of the duration of blood coagulation and an increase in the content of catecholamines and beta-lipoproteids occur.

Factors associated with coronary artery disease and stroke in adults with congenital heart disease.

PubMed

Bokma, Jouke P; Zegstroo, Ineke; Kuijpers, Joey M; Konings, Thelma C; van Kimmenade, Roland R J; van Melle, Joost P; Kiès, Philippine; Mulder, Barbara J M; Bouma, Berto J

2018-04-01

To determine factors associated with coronary artery disease (CAD) and ischaemic stroke in ageing adult congenital heart disease (ACHD) patients. We performed a multicentre case-control study, using data from the national CONgenital CORvitia (CONCOR) registry to identify ACHD patients within five participating centres. Patients with CAD were matched (1:2 ratio) with ACHD patients without CAD on age, CHD defect group and gender. Patients with ischaemic stroke (or transient ischaemic attack) were matched similarly. Medical charts were reviewed and a standardised questionnaire was used to determine presence of risk factors. Of 6904 ACHD patients, a total of 55 cases with CAD (80% male, mean age 55.1±12.4 years) and 56 cases with stroke (46% male, mean age 46.9±15.2) were included and matched with control patients. In multivariable logistic regression analysis, traditional atherosclerotic risk factors (hypertension (OR 2.45; 95% CI 1.15 to 5.23), hypercholesterolaemia (OR 3.99; 95% CI 1.62 to 9.83) and smoking (OR 2.25; 95% CI 1.09 to 4.66)) were associated with CAD. In contrast, these risk factors were not associated with ischaemic stroke. In multivariable analysis, stroke was associated with previous shunt operations (OR 4.20; 95% CI 1.36 to 12.9), residual/unclosed septal defects (OR 2.38; 95% CI 1.03 to 5.51) and left-sided mechanical valves (OR 2.67; 95% CI 1.09 to 6.50). Traditional atherosclerotic risk factors were associated with CAD in ACHD patients. In contrast, ischaemic stroke was related to factors (previous shunts, septal defects, mechanical valves) suggesting a cardioembolic aetiology. These findings may inform surveillance and prevention strategies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study.

PubMed

Pisano, Giuseppina; Fracanzani, Anna L; Caccamo, Lucio; Donato, Maria F; Fargion, Silvia

2016-10-28

Improved surgical techniques and greater efficacy of new anti-rejection drugs have significantly improved the survival of patients undergoing orthotopic liver transplantation (OLT). This has led to an increased incidence of metabolic disorders as well as cardiovascular and cerebrovascular diseases as causes of morbidity and mortality in OLT patients. In the last decade, several studies have examined which predisposing factors lead to increased cardiovascular risk ( i.e ., age, ethnicity, diabetes, NASH, atrial fibrillation, and some echocardiographic parameters) as well as which factors after OLT ( i.e ., weight gain, metabolic syndrome, immunosuppressive therapy, and renal failure) are linked to increased cardiovascular mortality. However, currently, there are no available data that evaluate the development of atherosclerotic damage after OLT. The awareness of high cardiovascular risk after OLT has not only lead to the definition of new but generally not accepted screening of high risk patients before transplantation, but also to the need for careful patient follow up and treatment to control metabolic and cardiovascular pathologies after transplant. Prospective studies are needed to better define the predisposing factors for recurrence and de novo occurrence of metabolic alterations responsible for cardiovascular damage after OLT. Moreover, such studies will help to identify the timing of disease progression and damage, which in turn may help to prevent morbidity and mortality for cardiovascular diseases. Our preliminary results show early occurrence of atherosclerotic damage, which is already present a few weeks following OLT, suggesting that specific, patient-tailored therapies should be started immediately post OLT.

Aorto-iliac occlusive disease in the different population groups--clinical pattern, risk profile and results of reconstruction.

PubMed

Madiba, T E; Mars, M; Robbs, J V

1999-12-01

It has previously been accepted that atherosclerotic disease is uncommon among blacks worldwide; however, recent studies have increasingly reported atherosclerotic disease in this group. Prospective study of hospital patients with aorto-iliac occlusive disease presenting to the vascular service of the Durban metropolitan hospitals. The study was designed to assess clinical pattern, risk profile and results of reconstruction in these patients. This is a study of 688 patients with aorto-iliac occlusive disease managed over 9 years in Durban, with clinical pattern and risk factors compared in the different population groups. A subgroup of 492 patients underwent aortobifemoral bypass, providing material for comparison of the results of reconstruction in the different population groups. More black patients presented with gangrene and threatened limb, whereas whites tended to present early with claudication. All groups had hypertension and diabetes as risk factors. In addition, whites and Indians had ischaemic heart disease, which was not found among blacks. Mortality was 5% (blacks 1.8%, whites 8.5%, Indians 5%). Medium-term occlusion rates were 19% in blacks, 13% in Indians and 5% among whites. Five-year cumulative patency rates were 92% for whites, 77% for Indians and 74% for blacks. Whites do significantly better than blacks, who tend to present at an advanced stage of the disease. The presence of ischaemic heart disease among whites and Indians contributes to the higher mortality in these groups.

Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis.

PubMed

Marthi, Amarnath; Donovan, Killian; Haynes, Richard; Wheeler, David C; Baigent, Colin; Rooney, Christopher M; Landray, Martin J; Moe, Sharon M; Yang, Jun; Holland, Lisa; di Giuseppe, Romina; Bouma-de Krijger, Annet; Mihaylova, Borislava; Herrington, William G

2018-05-15

Background Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD. Methods We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated. Results Depending on the assay used, median FGF-23 concentrations were 43-74 RU/ml and 38-47 pg/ml in 17 general population cohorts; 102-392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79-4212 RU/ml and 2526-5555 pg/ml in eight cohorts of patients on dialysis. Overall, comparing participants in the top and bottom FGF-23 concentration thirds, the summary RRs (95% confidence intervals [95% CIs]) were 1.33 (1.12 to 1.58) for myocardial infarction, 1.26 (1.13 to 1.41) for stroke, 1.48 (1.29 to 1.69) for heart failure, 1.42 (1.27 to 1.60) for cardiovascular mortality, and 1.70 (1.52 to 1.91) for all-cause mortality. The summary RR for noncardiovascular mortality, calculated indirectly, was 1.52 (95% CI, 1.28 to 1.79). When studies were ordered by average differences in FGF-23 concentration between the top and bottom thirds, there was no trend in RRs across the studies. Conclusions The similarly-sized associations between increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure-response relationship, suggest that the relationship between FGF-23 and cardiovascular disease risk may be noncausal. Copyright © 2018 by the American Society of Nephrology.

Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells.

PubMed

Aguilar, Edenil C; Santos, Lana Claudinez Dos; Leonel, Alda J; de Oliveira, Jamil Silvano; Santos, Elândia Aparecida; Navia-Pelaez, Juliana M; da Silva, Josiane Fernandes; Mendes, Bárbara Pinheiro; Capettini, Luciano S A; Teixeira, Lilian G; Lemos, Virginia S; Alvarez-Leite, Jacqueline I

2016-08-01

Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied. We investigated the influence of butyrate on oxidative status, reactive oxygen species (ROS) release and oxidative enzymes (NADPH oxidase and iNOS) in atherosclerotic lesions of ApoE(-/-) mice and in oxLDL-stimulated peritoneal macrophages and endothelial cells (EA.hy926). The lesion area in aorta was reduced while in the aortic valve, although lesion area was unaltered, superoxide production and protein nitrosylation were reduced in butyrate-supplemented mice. Peritoneal macrophages from the butyrate group presented a lower free radical release after zymosan stimulus. When endothelial cells were pretreated with butyrate before oxLDL stimulus, the CCL-2 and superoxide ion productions and NADPH oxidase subunit p22phox were reduced. In macrophage cultures, in addition to a reduction in ROS release, nitric oxide and iNOS expression were down-regulated. The data suggest that one mechanism related to the effect of butyrate on atherosclerotic development is the reduction of oxidative stress in the lesion site. The reduction of oxidative stress related to NADPH oxidase and iNOS expression levels associated to butyrate supplementation attenuates endothelium dysfunction and macrophage migration and activation in the lesion site. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiovascular risk-factor knowledge and risk perception among HIV-infected adults.

PubMed

Cioe, Patricia A; Crawford, Sybil L; Stein, Michael D

2014-01-01

Cardiovascular disease (CVD) has emerged as a major cause of morbidity and mortality in HIV-infected adults. Research in noninfected populations has suggested that knowledge of CVD risk factors significantly influences perceptions of risk. This cross-sectional study describes CVD risk factor knowledge and risk perception in HIV-infected adults. We recruited 130 HIV-infected adults (mean age = 48 years, 62% male, 56% current smokers, mean years since HIV diagnosis, 14.7). The mean CVD risk factor knowledge score was fairly high. However, controlling for age, CVD risk factor knowledge was not predictive of perceived risk [F(1, 117) = 0.13, p > .05]. Estimated risk and perceived risk were weakly but significantly correlated; r (126) = .24, p = .01. HIV-infected adults are at increased risk for CVD. Despite having adequate risk-factor knowledge, CVD risk perception was inaccurate. Improving risk perception and developing CVD risk reduction interventions for this population are imperative. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

A case of atherosclerotic inferior mesenteric artery aneurysm secondary to high flow state.

PubMed

Troisi, Nicola; Esposito, Giovanni; Cefalì, Pietro; Setti, Marco

2011-07-01

Inferior mesenteric artery aneurysms are very rare and they are among the rarest of visceral artery aneurysms. Sometimes, the distribution of the blood flow due to chronic atherosclerotic occlusion of some arteries can establish an increased flow into a particular supplying district (high flow state). A high flow state in a stenotic inferior mesenteric artery in compensation for a mesenteric occlusive disease can produce a rare form of aneurysm. We report the case of an atherosclerotic inferior mesenteric aneurysm secondary to high flow state (association with occlusion of the celiac trunk and severe stenosis of the superior mesenteric artery), treated by open surgical approach. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Modifiable risk factors for migraine progression.

PubMed

Bigal, Marcelo E; Lipton, Richard B

2006-10-01

Migraine is a chronic-recurrent disorder that progresses in some individuals. Transformed migraine is the result of this progression. Since migraine does not progress in most patients, identifying the risk factors for progression has emerged as a very important public health priority. If risk factors can be identified, that might provide a foundation for more aggressive preventive intervention. Risk factors for progression may be divided into non-remediable (gender, age, race) and remediable categories. In this paper, we focus on several already identified remediable risk factors, including frequency of migraine attacks, obesity, acute medication overuse, caffeine overuse, stressful life events, depression, and sleep disorders. We present the evidence for each risk factor and discuss possible interventions to address them.

Periodontitis is an independent risk indicator for atherosclerotic cardiovascular diseases among 60 174 participants in a large dental school in the Netherlands.

PubMed

Beukers, Nicky G F M; van der Heijden, Geert J M G; van Wijk, Arjen J; Loos, Bruno G

2017-01-01

The association between periodontitis and atherosclerotic cardiovascular diseases (ACVD) has been established in some modestly sized studies (<10 000). Rarely, however, periodontitis has been studied directly; often tooth loss or self-reported periodontitis has been used as a proxy measure for periodontitis. Our aim is to investigate the adjusted association between periodontitis and ACVD among all individuals registered in a large dental school in the Netherlands (Academic Centre for Dentistry Amsterdam (ACTA)). Anonymised data were extracted from the electronic health records for all registered patients aged >35 years (period 1998-2013). A participant was recorded as having periodontitis based on diagnostic and treatment codes. Any affirmative answer for cerebrovascular accidents, angina pectoris and/or myocardial infarction labelled a participant as having ACVD. Other risk factors for ACVD, notably age, sex, smoking, diabetes, hypertension, hypercholesterolaemia and social economic status, were also extracted. Logistic regression analyses were used to evaluate the adjusted associations between periodontitis and ACVD. 60 174 individuals were identified; 4.7% of the periodontitis participants (455/9730) and 1.9% of the non-periodontitis participants (962/50 444) reported ACVD; periodontitis showed a significant association with ACVD (OR 2.52; 95% CI 2.3 to 2.8). After adjustment for the confounders, periodontitis remained independently associated with ACVD (OR 1.59; 95% CI 1.39 to 1.81). With subsequent stratification for age and sex, periodontitis remained independently associated with ACVD. This cross-sectional analysis of a large cohort in the Netherlands of 60 174 participants shows the independent association of periodontitis with ACVD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Experience With Intravascular Ultrasound Imaging Of Human Atherosclerotic Arteries

NASA Astrophysics Data System (ADS)

Mallery, John A.; Gessert, James M.; Maciel, Mario; Tobis, John M.; Griffith, James M.; Berns, Michael W.; Henry, Walter L.

1989-08-01

Normal human arteries have a well-defined structure on intravascular images. The intima appears very thin and is most likely represented by a bright reflection arising from the internal elastic lamina. The smooth muscle tunica media is echo-lucent on the ultrasound image and appears as a dark band separating the intima from the adventitia. The adventitia is a brightly reflective layer of variable thickness. The thickness of the intima, and therefore of the atherosclerotic plaque can be accurately measured from the ultrasound images and correlates well with histology. Calcification within the wall of arteries is seen as bright echo reflection with shadowing of the peripheral wall. Fibrotic regions are highly reflective but do not shadow. Necrotic liquid regions within advanced atherosclerotic plaques are seen on ultrasound images as large lucent zones surrounded by echogenic tissue. Imaging can be performed before and after interventional procedures, such as laser angioplasty, balloon angioplasty and atherectomy. Intravascular ultrasound appears to provide an imaging modality for identifying the histologic characteristics of diseased arteries and for quantifying plaque thickness. It might be possible to perform such quantification to evaluate the results of interventional procedures.

Engineering adeno-associated virus 2 vectors for targeted gene delivery to atherosclerotic lesions.

PubMed

White, K; Büning, H; Kritz, A; Janicki, H; McVey, J; Perabo, L; Murphy, G; Odenthal, M; Work, L M; Hallek, M; Nicklin, S A; Baker, A H

2008-03-01

Targeted delivery of biological agents to atherosclerotic plaques may provide a novel treatment and/or useful tool for imaging of atherosclerosis in vivo. However, there are no known viral vectors that possess the desired tropism. Two plaque-targeting peptides, CAPGPSKSC (CAP) and CNHRYMQMC (CNH) were inserted into the capsid of adeno-associated virus 2 (AAV2) to assess vector retargeting. AAV2-CNH produced significantly higher levels of transduction than unmodified AAV2 in human, murine and rat endothelial cells, whereas transduction of nontarget HeLa cells was unaltered. Transduction studies and surface plasmon resonance suggest that AAV2-CNH uses membrane type 1 matrix metalloproteinase as a surface receptor. AAV2-CAP only produced higher levels of transduction in rat endothelial cells, possibly because the virus was found to be affected by proteasomal degradation. In vivo substantially higher levels of both peptide-modified AAV2 vectors was detected in the brachiocephalic artery (site of advanced atherosclerotic plaques) and aorta, whereas reduced levels were detected in all other organs examined. These results suggest that in the AAV2 platform the peptides are exposed on the capsid surface in a way that enables efficient receptor binding and so creates effective atherosclerotic plaque targeted vectors.

Effect of Watermarking on Diagnostic Preservation of Atherosclerotic Ultrasound Video in Stroke Telemedicine.

PubMed

Dey, Nilanjan; Bose, Soumyo; Das, Achintya; Chaudhuri, Sheli Sinha; Saba, Luca; Shafique, Shoaib; Nicolaides, Andrew; Suri, Jasjit S

2016-04-01

Embedding of diagnostic and health care information requires secure encryption and watermarking. This research paper presents a comprehensive study for the behavior of some well established watermarking algorithms in frequency domain for the preservation of stroke-based diagnostic parameters. Two different sets of watermarking algorithms namely: two correlation-based (binary logo hiding) and two singular value decomposition (SVD)-based (gray logo hiding) watermarking algorithms are used for embedding ownership logo. The diagnostic parameters in atherosclerotic plaque ultrasound video are namely: (a) bulb identification and recognition which consists of identifying the bulb edge points in far and near carotid walls; (b) carotid bulb diameter; and (c) carotid lumen thickness all along the carotid artery. The tested data set consists of carotid atherosclerotic movies taken under IRB protocol from University of Indiana Hospital, USA-AtheroPoint™ (Roseville, CA, USA) joint pilot study. ROC (receiver operating characteristic) analysis was performed on the bulb detection process that showed an accuracy and sensitivity of 100 % each, respectively. The diagnostic preservation (DPsystem) for SVD-based approach was above 99 % with PSNR (Peak signal-to-noise ratio) above 41, ensuring the retention of diagnostic parameter devalorization as an effect of watermarking. Thus, the fully automated proposed system proved to be an efficient method for watermarking the atherosclerotic ultrasound video for stroke application.

Lower limb atherosclerotic disease causes various deteriorations of patients' health-related quality of life.

PubMed

Koivunen, Kirsi; Lukkarinen, Hannele

2006-12-01

Lower limb atherosclerotic disease (LLAD) is a worldwide health problem. Approximately 100,000 Finns have LLAD. Currently, a large number of health-related quality of life (HRQoL) studies are available, but we still have scant comprehensive information of HRQoL of patients with LLAD. The aim was to describe the HRQoL of women and men with LLAD in relation to the age- and sex-matched general population. In addition, the purpose was to study which demographic and relevant clinical and psychologic factors are connected with HRQoL of patients with LLAD. Patients with LLAD (N = 180, 62 women and 118 men) were recruited to participate in this study in the Clinic of Surgery, Oulu University Hospital, from 2001 to 2004. The control sample consisted of an age- and sex-matched general population (N = 2126; 1081 women and 1045 men). The HRQoL of the women and men with LLAD was evaluated using the Nottingham Health Profile (NHP) instrument, in relation to an age- and sex-matched general population (N = 2126) as well as demographic and relevant clinical and psychologic factors. The HRQoL of men was significantly (P < .05) poorer on all dimensions of the NHP instrument in the age groups 55 to 74 years. HRQoL was also clearly affected in the youngest age group of men on the dimensions of pain (P < .05) and mobility (P < .05) and further in the oldest age group on the dimension of energy (P < .05). The HRQoL of women with LLAD was only significantly poorer (P < .05) on the dimension of pain in the age group of 65 to 74 years than the HRQoL of age-matched Finnish women. The most emphasized relationships between poor HRQoL and the demographic, relevant clinical and psychologic factors were male sex, lack of exercise, retirement, a short painless walking distance, other atherosclerotic disease, poor subjective health status, problems with ability to cope at home, problems with the treatment of illness, and sex life. Male patients with LLAD had poorer HRQoL than the corresponding

Role of six single nucleotide polymorphisms, risk factors in coronary disease, in OLR1 alternative splicing

PubMed Central

Tejedor, J. Ramón; Tilgner, Hagen; Iannone, Camilla; Guigó, Roderic; Valcárcel, Juan

2015-01-01

The OLR1 gene encodes the oxidized low-density lipoprotein receptor (LOX-1), which is responsible for the cellular uptake of oxidized LDL (Ox-LDL), foam cell formation in atheroma plaques and atherosclerotic plaque rupture. Alternative splicing (AS) of OLR1 exon 5 generates two protein isoforms with antagonistic functions in Ox-LDL uptake. Previous work identified six single nucleotide polymorphisms (SNPs) in linkage disequilibrium that influence the inclusion levels of OLR1 exon 5 and correlate with the risk of cardiovascular disease. Here we use minigenes to recapitulate the effects of two allelic series (Low- and High-Risk) on OLR1 AS and identify one SNP in intron 4 (rs3736234) as the main contributor to the differences in exon 5 inclusion, while the other SNPs in the allelic series attenuate the drastic effects of this key SNP. Bioinformatic, proteomic, mutational and functional high-throughput analyses allowed us to define regulatory sequence motifs and identify SR protein family members (SRSF1, SRSF2) and HMGA1 as factors involved in the regulation of OLR1 AS. Our results suggest that antagonism between SRSF1 and SRSF2/HMGA1, and differential recognition of their regulatory motifs depending on the identity of the rs3736234 polymorphism, influence OLR1 exon 5 inclusion and the efficiency of Ox-LDL uptake, with potential implications for atherosclerosis and coronary disease. PMID:25904137

Dietary saturated fat intake and atherosclerotic vascular disease mortality in elderly women: a prospective cohort study.

PubMed

Blekkenhorst, Lauren C; Prince, Richard L; Hodgson, Jonathan M; Lim, Wai H; Zhu, Kun; Devine, Amanda; Thompson, Peter L; Lewis, Joshua R

2015-06-01

The reduction of saturated fatty acid (SFA) intake has been the basis of long-standing dietary recommendations. However, recent epidemiologic studies have reported conflicting evidence in the relation between SFA consumption and risk of atherosclerotic vascular disease (ASVD) mortality. We investigated the association of SFA intake with serum lipid profiles and ASVD mortality in a population-based 10-y cohort study. At baseline (1998) 1469 women living in Perth, Western Australia, with a mean ± SD age of 75.2 ± 2.7 y had SFA intake measured by using a validated food-frequency questionnaire. Outcome data were serum lipids at baseline and ASVD deaths over 10 y (13,649 person-years of follow-up), retrieved from the Western Australian Data Linkage System. Other risk factors for ASVD were assessed and adjusted for in multivariable analyses. ASVD deaths occurred in 9.1% (134) of participants. The highest quartile of SFA intake (>31.28 g/d) had an ~16% cumulative mortality risk compared with ~5% in the lowest quartile (<17.39 g/d) (HR: 3.07; 95% CI: 1.54, 6.11; P = 0.001). Baseline SFA intake was associated with baseline serum total and LDL cholesterol in multivariable-adjusted models (β: 0.199, SE: 0.056, P < 0.001 and β: 0.190, SE: 0.051, P < 0.001, respectively). However, baseline serum total and LDL cholesterol were not associated with ASVD mortality. High SFA intake was associated with the risk of ASVD mortality in this population of elderly women. Although there was a strong positive association between SFA intake and LDL cholesterol, LDL cholesterol was not associated with ASVD mortality in this cohort. Nevertheless, these data support dietary advice to reduce SFA intake. © 2015 American Society for Nutrition.

Sociodemographic factors associated with multiple cardiovascular risk factors among Malaysian adults.

PubMed

Ghazali, Sumarni Mohd; Seman, Zamtira; Cheong, Kee Chee; Hock, Lim Kuang; Manickam, Mala; Kuay, Lim Kuang; Yusoff, Ahmad Faudzi; Mustafa, Feisul Idzwan; Mustafa, Amal Nasir

2015-01-31

To determine the prevalence and sociodemographic correlates of multiple risk factors for cardiovascular disease (CVD) among Malaysian adults. We analysed data on 1044 men and 1528 women, aged 24-64 years, participants in the Non Communicable Disease Surveillance 2005/2006, a nationally representative, population-based, cross-sectional study. Prevalence of obesity, high blood pressure, dyslipidaemia, hyperglycemia, physical inactivity, smoking, risky drinking, low vegetable and fruit intake were determined and multivariable logistic regression was used to identify sociodemographic factors associated with having ≥3 of these cardiovascular disease risk factors. The response rate was 84.6% (2572/3040). Overall, 68.4% (95% CI: 63.2, 73.1) had at least three risk factors. Among men, older age and Indian ethnicity were independently associated with having ≥3 CVD risk factors; while among women, older age, low education, and housewives were more likely to have ≥3 CVD risk factors. The prevalence of cardiovascular risk factors clustering among Malaysian adults is high, raising concerns that cardiovascular disease incidence will rise steeply in the near future if no immediate preventive measures are taken. The current national health education and promotion programmes pertaining to modifiable risk factors can be further improved by taking into account the sociodemographic variation in CVD risk factors clustering.

Haploinsufficiency of E-selectin ligand-1 is Associated with Reduced Atherosclerotic Plaque Macrophage Content while Complete Deficiency Leads to Early Embryonic Lethality in Mice

PubMed Central

Luo, Wei; Wang, Hui; Guo, Chiao; Wang, Jintao; Kwak, Jeffrey; Bahrou, Kristina L; Eitzman, Daniel T.

2012-01-01

E-selectin-1 (ESL-1), also known as golgi complex-localized glycoprotein-1 (GLG1), homocysteine-rich fibroblast growth factor receptor (CGR-1), and latent transforming growth factor-β complex protein 1 (LTCP-1), is a multifunctional protein with widespread tissue distribution. To determine the functional consequences of ESL-1 deficiency, mice were generated carrying an ESL-1 gene trap. After backcrossing to C57BL6/J for 6 generations, mice heterozygous for the gene trap (ESL-1+/-) were intercrossed to produce ESL-1-/- mice, however ESL-1-/- mice were not viable, even at embryonic day E10.5. To determine the effect of heterozygous ESL-1 deficiency on atherosclerosis, apolipoprotein E deficient (ApoE-/-), ESL-1+/- mice were generated and fed western diet. Compared to ApoE-/-, ESL-1++ mice, atherosclerotic lesions from ApoE-/-, ESL-1+/- contained more collagen and fewer macrophages, suggesting increased plaque stability. In conclusion, heterozygous deficiency of ESL-1 is associated with features of increased atherosclerotic plaque stability while complete deficiency of ESL-1 leads to embryonic lethality. PMID:22939356

Quantifying cardiometabolic risk using modifiable non-self-reported risk factors.

PubMed

Marino, Miguel; Li, Yi; Pencina, Michael J; D'Agostino, Ralph B; Berkman, Lisa F; Buxton, Orfeu M

2014-08-01

Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. To develop and validate a cumulative general cardiometabolic risk score that focuses on non-self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut-off points for risk categories. We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14-year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender-specific Cox proportional hazards models were considered to evaluate the effects of non-self-reported modifiable risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10-year general cardiometabolic risk score functions and evaluated its predictive performance in 2012-2013. HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit chi-square=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk on the basis of modifiable risk factors that can motivate an individual's commitment to prevention and intervention. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Quantifying Cardiometabolic Risk Using Modifiable Non–Self-Reported Risk Factors

PubMed Central

Marino, Miguel; Li, Yi; Pencina, Michael J.; D’Agostino, Ralph B.; Berkman, Lisa F.; Buxton, Orfeu M.

2014-01-01

Background Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. Purpose To develop and validate a cumulative general cardiometabolic risk score that focuses on non–self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut off points for risk categories. Methods We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14–year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender–specific Cox proportional hazards models were considered to evaluate the effects of non–self-reported modifiable risk factors (blood pressure, total cholesterol, high–density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10–year general cardiometabolic risk score functions and evaluated its predictive performance in 2012–2013. Results HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit χ2=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). Conclusions This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk based on modifiable risk factors that can motivate an individual’s commitment to prevention and intervention. PMID:24951039

Gold nanoparticles based imaging technique and drug delivery for the detection and treatment of atherosclerotic vascular disease

NASA Astrophysics Data System (ADS)

Ankri, Rinat; Leshem-Lev, Dorit; Lev, Eli I.; Motiei, Menachem; Hochhauser, Edith; Fixler, Dror

2016-03-01

In our study we aim to develop a new, simple and non-invasive method to detect and to treat atherosclerosis. We use gold nanoparticles (GNPs) combined with the diffusion reflection (DR) method to demonstrate the detection of vulnerable atherosclerotic plaques. Our method is based on the fact that macrophages are a major component in the vulnerable plaque and are able to uptake metal nanoparticles that can be discovered by the DR system. Moreover, it is well known that high density lipoprotein (HDL) reduces ASVD by inhibiting pro-inflammatory factors, enabling the specific treatment of atherosclerosis.

Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1.

PubMed Central

Johnson-Tidey, R. R.; McGregor, J. L.; Taylor, P. R.; Poston, R. N.

1994-01-01

P-selectin (GMP-140) is an adhesion molecule present within endothelial cells that is rapidly translocated to the cell membrane upon activation, where it mediates endothelial-leukocyte interactions. Immunohistochemical analysis of human atherosclerotic plaques has shown strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques. P-selectin is not, however, detected in normal arterial endothelium or in endothelium overlying inactive fibrous plaques. Color image analysis was used to quantitate the degree of P-selectin expression in the endothelium and demonstrates a statistically significant increase in P-selectin expression by atherosclerotic endothelial cells. Double immunofluorescence shows that some of this P-selectin is expressed on the luminal surface of the endothelial cells. Previous work has demonstrated a significant up-regulation in the expression of the intercellular adhesion molecule-1 in atherosclerotic endothelium and a study on the expression of intercellular adhesion molecule-1 and P-selectin in atherosclerosis shows a highly positive correlation. These results suggest that the selective and cooperative expression of P-selectin and intercellular adhesion molecule-1 may be involved in the recruitment of monocytes into sites of atherosclerosis. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:7513951

Inhalation exposure of gas-metal arc stainless steel welding fume increased atherosclerotic lesions in apolipoprotein E knockout mice.

PubMed

Erdely, Aaron; Hulderman, Tracy; Salmen-Muniz, Rebecca; Liston, Angie; Zeidler-Erdely, Patti C; Chen, Bean T; Stone, Samuel; Frazer, David G; Antonini, James M; Simeonova, Petia P

2011-07-04

Epidemiological studies suggest that welding, a process which generates an aerosol of inhalable gases and metal rich particulates, increases the risk for cardiovascular disease. In this study we analyzed systemic inflammation and atherosclerotic lesions following gas metal arc-stainless steel (GMA-SS) welding fume exposure. Apolipoprotein E knockout (apoE(-/-)) mice, fed a Western diet, were exposed to GMA-SS at 40mg/m(3) for 3h/day for ten days (∼8.26μg daily alveolar deposition). Mice were sacrificed two weeks after exposure and serum chemistry, serum protein profiling and aortic lesion area were determined. There were no significant changes in serum total cholesterol, triglycerides or alanine aminotransferase. Serum levels of uric acid, a potent antioxidant, were decreased perhaps suggesting a reduced capacity to combat systemic oxidative stress. Inflammatory serum proteins interleukin 1 beta (IL-1β) and monocyte chemoattractant protein 3 (MCP-3) were increased two weeks after GMA-SS exposure. Analysis of atherosclerotic plaques showed an increase in lesion area as the result of GMA-SS exposure. In conclusion, GMA-SS exposure showed evidence of systemic inflammation and increased plaque progression in apoE(-/-) mice. These results complement epidemiological and functional human studies that suggest welding may result in adverse cardiovascular effects. Published by Elsevier Ireland Ltd.

Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Liu, Kathleen D; Yang, Wei; Go, Alan S; Anderson, Amanda H; Feldman, Harold I; Fischer, Michael J; He, Jiang; Kallem, Radhakrishna R; Kusek, John W; Master, Stephen R; Miller, Edgar R; Rosas, Sylvia E; Steigerwalt, Susan; Tao, Kaixiang; Weir, Matthew R; Hsu, Chi-Yuan

2015-02-01

Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria). Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. 3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008. Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011. Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. Urine NGAL was measured only once. Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths. Copyright © 2015 National Kidney Foundation, Inc. All rights

Effects of age and cardiovascular risk factors on (18)F-FDG PET/CT quantification of atherosclerosis in the aorta and peripheral arteries.

PubMed

Pasha, Ahmed K; Moghbel, Mateen; Saboury, Babak; Gharavi, Mohammed H; Blomberg, Björn A; Torigian, Drew A; Kwee, Thomas C; Basu, Sandip; Mohler Iii, Emile R; Alavi, Abass

2015-01-01

To quantify fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in the aorta and peripheral arteries and assess the variation of (18)F-FDG uptake with age and cardiovascular risk factors. The subject population of this retrospective study comprises melanoma patients who underwent whole-body (18)F-FDG PET/CT scans. The patients' medical records were examined for cardiovascular risk factors and for a history of coronary artery disease or peripheral artery disease. Fluorine-18-FDG uptake in the peripheral arteries (iliac and femoral) and aorta was semi-quantified as a weighted-average mean standardized uptake value (wA-SUVmean), while background noise was accounted for by measuring mean venous blood pool SUV (V-SUVmean) in the superior vena cava. Atherosclerosis was semi-quantified by the tissue-to-background ratio (TBR) (wA-SUVmean divided by V-SUVmean). A regression model and t-test were used to evaluate the effect of age and location on the degree of atherosclerosis. To assess the effect of cardiovascular risk factors on atherosclerotic burden, the wA-SUVmean of patients with at least one of these risk factors was compared to that of patients without any risk factors. A total of 76 patients (46 men, 30 women; 22-91 years old) were included in this study. The average TBR of the aorta and peripheral arteries were 2.68 and 1.43, respectively, and increased with age in both locations. In regression analysis, the beta coefficients of age for TBR in the aorta and peripheral arteries were 0.55 (P<0.001) and 0.03 (P<0.001), respectively. In all age groups, the TBR of the aorta was significantly greater than that of the peripheral arteries. The Pearson correlation coefficients between the four age groups and the TBR of the aorta and peripheral arteries were 0.83 (P<0.001) and 0.75 (P<0.001), respectively. The wA-SUVmean of patients with cardiovascular risk factors was only significant (P<0.05) in the aorta. An increase in (18)F-FDG uptake was observed in the peripheral

Rapid noninvasive detection of experimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates

PubMed Central

Elmaleh, David R.; Narula, Jagat; Babich, John W.; Petrov, Artiom; Fischman, Alan J.; Khaw, Ban-An; Rapaport, Eliezer; Zamecnik, Paul C.

1998-01-01

The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5′)-tetraphosphate) and its analogue 99mTc AppCHClppA for imaging experimental atherosclerotic lesions in New Zealand White rabbits. Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides. After acquiring the final images, the animals were sacrificed, ex vivo images of the aortas were recorded, and biodistribution was measured. 99mTc-Ap4A and 99mTc AppCHClppA accumulated rapidly in atherosclerotic abdominal aorta, and lesions were clearly visible within 30 min after injection in all animals that were studied. Both radiopharmaceuticals were retained in the lesions for 3 hr, and the peak lesion to normal vessel ratio was 7.4 to 1. Neither of the purine analogs showed significant accumulation in the abdominal aorta of normal (control) rabbits. The excised aortas showed lesion patterns that were highly correlated with the in vivo and ex vivo imaging results. The present study demonstrates that purine receptors are up-regulated in experimental atherosclerotic lesions and 99mTc-labeled purine analogs have potential for rapid noninvasive detection of plaque formation. PMID:9435254

High purity tocotrienols attenuate atherosclerotic lesion formation in apoE-KO mice.

PubMed

Shibata, Akira; Kobayashi, Teiko; Asai, Akira; Eitsuka, Takahiro; Oikawa, Shinichi; Miyazawa, Teruo; Nakagawa, Kiyotaka

2017-10-01

Previous studies have demonstrated that tocotrienol (T3) has antiatherogenic effects. However, the T3 preparations used in those studies contained considerable amounts of tocopherol (Toc), which might affect the biological activity of T3. There is little information on the effect of highly purified T3 on atherosclerosis formation. This study investigated the effect of high-purity T3 on atherosclerotic lesion formation and the underlying mechanisms. Male apolipoprotein E knockout (apoE-KO) mice were fed a cholesterol-containing diet either alone or supplemented with T3 concentrate (Toc-free T3) or with α-Toc for 12 weeks. ApoE-KO mice fed the 0.2% T3-supplemented diet showed reduced atherosclerotic lesion formation in the aortic root. The 0.2% T3 diet induced Slc27a1 and Ldlr gene expression levels in the liver, whereas the α-Toc-supplemented diet did not affect those expression levels. T3 was predominantly deposited in fat tissue in the T3 diet-fed mice, whereas α-Toc was preferentially accumulated in liver in the α-Toc diet-fed mice. Considered together, these data demonstrate that dietary T3 exerts anti-atherosclerotic effect in apoE-KO mice. The characteristic tissue distribution and biological effects of T3, that are substantially different from those of Toc, may contribute to the antiatherogenic properties of T3. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk Factors and Causes of Syncope

MedlinePlus

... Risk Factors & Causes of Syncope Risk Factors for Cardiovascular Syncope The risk of cardiovascular syncope increases with ... Long QT syndrome and Brugada Syndrome Signs of Cardiovascular Syncope Cardiovascular syncope usually is sudden. There may ...

Overexpression of hypoxia/inflammatory markers in atherosclerotic carotid plaques.

PubMed

Luque, Ana; Turu, Marta; Juan-Babot, Oriol; Cardona, Pere; Font, Angels; Carvajal, Ana; Slevin, Mark; Iborra, Elena; Rubio, Francisco; Badimon, Lina; Krupinski, Jerzy

2008-05-01

Hypoxia, angiogenesis and inflammation leads to plaque progression and remodelling and may significantly contribute towards plaque rupture and subsequent cerebrovascular events. Our aim was to study, markers of hypoxia and inflammation previously identified by microarray analysis, in atherosclerotic carotid arteries with low to moderate stenosis. We hoped to describe different cellular populations expressing the studied markers. The location of selected inflammatory molecules obtained as vascular transplants from organ donors were analysed by immunohistochemistry with monoclonal and polyclonal antibodies. Paraffin-embedded sections were cut and probed with antibodies recognizing active B and T-lymphocytes (CD30), hypoxia-inducible factor-1alpha, endoglin (CD105), Interleukin-6 and C-reactive protein. We observed a notable overexpression of HIF-1alpha in inflammatory and hypoxic areas of carotid arteries in all types of lesions from type II-V taken from the patients with carotid stenosis less than 50%. This suggests that HIF-1alpha may have a putative role in atherosclerosis progression and angiogenesis. Dynamic changes in the non-occluding plaques may explain some of the clinical events in patients with low to moderate carotid stenosis.

Population distribution of traditional and the emerging cardiovascular risk factors carotid plaque and IMT: the REFINE-Reykjavik study with comparison with the Tromsø study

PubMed Central

Thorsson, Bolli; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Gudmundsson, Elias Freyr; Bots, Michael L; Aspelund, Thor; Arntzen, Kjell Arne; Mathiesen, Ellisiv B; Gudnason, Vilmundur

2018-01-01

Objectives Population statistics for carotid plaque and cardiovascular risk factors reported in scientific journals are usually presented as averages for the population or age and sex adjusted, rather than sex and age groups. Important population differences about atherosclerosis and cardiovascular risk factors may thus be missed. We compare the distribution of cardiovascular risk factors, carotids plaque and carotid intima-media thickness (CIMT) in two population-based studies. Methods Carotid artery atherosclerotic plaque prevalence and risk factors levels for cardiovascular disease by sex in 5-year age groups from the Risk Evaluation For Infarct Estimates Reykjavik study (REFINE-Reykjavik study) were compared with data from the Tromsø 6 study. Results The threshold of carotid plaque presence in the Tromsø 6 study fell between minimal and moderate plaque defined in the REFINE-Reykjavik study reflecting carotid plaque prevalence. The prevalence of minimal carotid plaque in the REFINE-Reykjavik study was 47% in men (40–69 years old) and 38% in women and 11% in men and 7% in women of moderate plaque. The prevalence of any plaque in the Tromsø 6 study was 35% in men and 27% in women. The mean (CIMT) was similar in the studies. In the Tromsø 6 study mean systolic blood pressure was 8 mm Hg higher in men and 10 mm Hg higher in women, mean low-density lipoprotein was 0.5 mmol/L higher in men and 0.3 mmol/L higher in women and the prevalence of smoking was 4% higher in men and 9% higher in women. However, body mass index was 0.8 kg/m2 higher in men and 0.9 kg/m2 in women in the REFINE-Reykjavik study. Conclusion Comparison between Iceland and Norway revealed differences in the prevalence of carotid plaque, which was assumed to be due to different definition of plaque. However, clinically significant differences in conventional cardiovascular risk factors were seen. This underscores the importance of detailed comparison of population data across

Dietary habits and risk factors for atherosclerosis in students from Bento Gonçalves (state of Rio Grande do Sul).

PubMed

Cimadon, Hosana Maria Speranza; Geremia, Renata; Pellanda, Lucia Campos

2010-08-01

Atherosclerotic cardiovascular disease begins its process in early childhood and is influenced throughout life by genetic factors and environmental exposure to potentially modifiable risk factors. To investigate the prevalence of risk factors for atherosclerosis with emphasis on dietary habits in a predominantly Italian colonization town. Population-based cross sectional study, involving 590 primary school students aged between 9 and 18 years, with a cluster sample. The following were collected: identification data, family history and personal history, and information regarding students' eating habits. Dietary habits considered inappropriate included: consumption of fast food, sugary snacks, sugar-sweetened beverages and animal fats four or more times a week, and fruits, green vegetables, and leguminous vegetables less than four times a week. The prevalence of overweight among students was 24.6% (n = 145), high blood pressure, 11.1% (n = 65); passive smoking, 35.4% (n = 208); sedentary lifestyle, 52.3% (n = 306), family history of 1st degree disease: hypertension, 21.4%, obesity 36.5%. Food items eaten four or more times a week: fast food, 70.3% (n = 411); sugary snacks, 42.7% (n = 252), sugar-sweetened beverages, 71% (n = 419), and animal fats, 24.4% (n = 143). Food items eaten less than four times a week: fruits, 36.8% (n = 215), green vegetables, 49.5% (n = 292) and leguminous vegetables, 63.7% (n = 374). Interventions are needed to promote changes in students' eating habits: higher level of consumption of fruits, green vegetables and leguminous vegetables, and increased level of physical activity.

Association between serum N-terminal pro-B-type natriuretic peptide levels and characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography.

PubMed

Gan, Lu; Feng, Cong; Liu, Chunlei; Tian, Shuping; Song, Xiang; Yang, Li

2016-08-01

The aim of the present study was to explore the association between the levels of serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and the characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography (CCTA), in patients with unstable angina (UA). A total of 202 patients (age range, 47-82 years) were divided into the following three groups: Non-cardiac disease group (57 patients); stable angina pectoris (SAP) group (62 patients); and UA group (83 patients). There were significant differences between the serum NT-pro BNP levels among the three groups (P=0.007). However, in multivariant diagnoses, NT-pro BNP level was not an independent risk factor for UA. The levels of serum NT-pro BNP were observed to be positively correlated with the number of vessels involved (r=0.462; P<0.001), SIS (r=0.475; P<0.001), segment-stenosis score (r=0.453; P<0.001), coronary calcification score (r=0.412; P=0.001), number of obstructive diseases (r=0.346; P<0.001), and the number of segments with non-calcified plaque (r=0.235; P=0.017), mixed plaque (r=0.234; P=0.017) and calcified plaque (r=0.431; P<0.001). The levels of serum NT-pro BNP were significantly higher in patients with UA and left main-left anterior descending (LM-LAD) disease, compared with UA patients without LM-LAD disease (P<0.001). In addition, serum NT-pro BNP was significantly higher in patients with obstructive disease and UA than in those without obstructive disease (P<0.001). The area under the curve of log(NT-pro BNP) was 0.656 (P=0.006; optimal cut-off value, 1.74; sensitivity, 77.6%; specificity, 51.9%). In conclusion, the levels of serum NT-pro BNP are associated with the burden and severity of coronary artery atherosclerotic disease in patients with UA, and may be helpful in risk stratification of patients with UA.

Association between serum N-terminal pro-B-type natriuretic peptide levels and characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography

PubMed Central

Gan, Lu; Feng, Cong; Liu, Chunlei; Tian, Shuping; Song, Xiang; Yang, Li

2016-01-01

The aim of the present study was to explore the association between the levels of serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and the characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography (CCTA), in patients with unstable angina (UA). A total of 202 patients (age range, 47–82 years) were divided into the following three groups: Non-cardiac disease group (57 patients); stable angina pectoris (SAP) group (62 patients); and UA group (83 patients). There were significant differences between the serum NT-pro BNP levels among the three groups (P=0.007). However, in multivariant diagnoses, NT-pro BNP level was not an independent risk factor for UA. The levels of serum NT-pro BNP were observed to be positively correlated with the number of vessels involved (r=0.462; P<0.001), SIS (r=0.475; P<0.001), segment-stenosis score (r=0.453; P<0.001), coronary calcification score (r=0.412; P=0.001), number of obstructive diseases (r=0.346; P<0.001), and the number of segments with non-calcified plaque (r=0.235; P=0.017), mixed plaque (r=0.234; P=0.017) and calcified plaque (r=0.431; P<0.001). The levels of serum NT-pro BNP were significantly higher in patients with UA and left main-left anterior descending (LM-LAD) disease, compared with UA patients without LM-LAD disease (P<0.001). In addition, serum NT-pro BNP was significantly higher in patients with obstructive disease and UA than in those without obstructive disease (P<0.001). The area under the curve of log(NT-pro BNP) was 0.656 (P=0.006; optimal cut-off value, 1.74; sensitivity, 77.6%; specificity, 51.9%). In conclusion, the levels of serum NT-pro BNP are associated with the burden and severity of coronary artery atherosclerotic disease in patients with UA, and may be helpful in risk stratification of patients with UA. PMID:27446259

Vertigo and dizziness in adolescents: Risk factors and their population attributable risk.

PubMed

Filippopulos, Filipp M; Albers, Lucia; Straube, Andreas; Gerstl, Lucia; Blum, Bernhard; Langhagen, Thyra; Jahn, Klaus; Heinen, Florian; von Kries, Rüdiger; Landgraf, Mirjam N

2017-01-01

To assess potential risk factors for vertigo and dizziness in adolescents and to evaluate their variability by different vertigo types. The role of possible risk factors for vertigo and dizziness in adolescents and their population relevance needs to be addressed in order to design preventive strategies. The study population consisted of 1482 school-children between the age of 12 and 19 years, who were instructed to fill out a questionnaire on different vertigo types and related potential risk factors. The questionnaire specifically asked for any vertigo, spinning vertigo, swaying vertigo, orthostatic dizziness, and unspecified dizziness. Further a wide range of potential risk factors were addressed including gender, stress, muscular pain in the neck and shoulder region, sleep duration, migraine, coffee and alcohol consumption, physical activity and smoking. Gender, stress, muscular pain in the neck and shoulder region, sleep duration and migraine were identified as independent risk factors following mutual adjustment: The relative risk was 1.17 [1.10-1.25] for female sex, 1.07 [1.02-1.13] for stress, 1.24 [1.17-1.32] for muscular pain, and 1.09 [1.03-1.14] for migraine. The population attributable risk explained by these risk factors was 26%, with muscular pain, stress, and migraine accounting for 11%, 4%, and 3% respectively. Several established risk factors in adults were also identified in adolescents. Risk factors amenable to prevention accounted for 17% of the total population risk. Therefore, interventions targeting these risk factors may be warranted.

Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles

USDA-ARS?s Scientific Manuscript database

Current approaches to the diagnosis and therapy of atherosclerosis cannot target to lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing in...

Advanced oxidation protein products and their relationship with cardiovascular risk factors in young apparently healthy people.

PubMed

Villalpando Sánchez, Diana Carolina; Alvarez Aguilar, Cleto; Gómez García, Anel

Advanced oxidation protein products (AOPPs) are used as a marker to estimate oxidative stress in plasma proteins. Oxidative stress is considered a factor of cardiovascular risk (CVRF) related to increased blood pressure, and dyslipidaemia. The aim of this study was to evaluate the association between plasma AOPPs and CVRF in apparently healthy young adults. A prospective cross-sectional study was conducted on 120 students of the Faculty of Chemical-Pharmacobiology of the UMSNH. Body mass index (BMI) and blood pressure were determined. A blood specimen was also collected to quantify AOPPs, glucose, total cholesterol, lipoproteins (high, low, and very low density), and triglycerides. Differences were observed in the groups with and without CVRF, with significant differences in BMI, waist, body fat (P<.05), and lipid profile (P<.0001). AOPPs were higher in the group of young people with three and four CVRF (F: 4.651; P=.002). A negatively correlation was found between AOPPs and LDL cholesterol (r=-0.364; P=.0001). It was observed that AOPPs concentrations are increased as CVRF increase in young adults. Thus, this could be considered an important risk factor, because their deposition in the atherosclerotic plaque favours the atherogenic process, and thus the development of cardiovascular disease. Quantification of AOPPs contributes to the indirect determination of oxidative status in the body. The study of metabolic and oxidative state of apparently healthy young adults is important in the prevention of cardiovascular disease in later life. More longitudinal studies are required to study its evolution. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Folic Acid Supplementation Delays Atherosclerotic Lesion Development by Modulating MCP1 and VEGF DNA Methylation Levels In Vivo and In Vitro

PubMed Central

Cui, Shanshan; Li, Wen; Lv, Xin; Wang, Pengyan; Gao, Yuxia; Huang, Guowei

2017-01-01

The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells. We analyzed atherosclerotic lesion histology, folate concentration, homocysteine concentration, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and DNA methyltransferase activity, as well as monocyte chemotactic protein-1 (MCP1) and vascular endothelial growth factor (VEGF) expression and promoter methylation. Folic acid reduced atherosclerotic lesion size in ApoE knockout mice. The underlying folic acid protective mechanism appears to operate through regulating the normal homocysteine state, upregulating the SAM: SAH ratio, elevating DNA methyltransferase activity and expression, altering MCP1 and VEGF promoter methylation, and inhibiting MCP1 and VEGF expression. We conclude that folic acid supplementation effectively prevented atherosclerosis by modifying DNA methylation through the methionine cycle, improving DNA methyltransferase activity and expression, and thus changing the expression of atherosclerosis-related genes. PMID:28475147

[Prevalence of cardiovascular risk factors in adolescents].

PubMed

Romanzini, Marcelo; Reichert, Felipe Fossati; Lopes, Adair da Silva; Petroski, Edio Luiz; de Farias Júnior, José Cazuza

2008-11-01

The aim of this study was to determine the prevalence of cardiovascular risk factors in adolescents and to verify its association with age and gender. 644 high school students from public schools in the city of Londrina, Paraná State, Brazil, participated in the study. A two-step sampling process was used. Behavioral risk factors (physical inactivity, inadequate consumption of fruits and vegetables, and smoking) and biological risk factors (overweight and high blood pressure) were investigated. Nearly 90% of adolescents showed at least one risk factor. Inadequate consumption of fruits (56.7%) and vegetables (43.9%) and physical inactivity (39.2%) were the most prevalent risk factors. Prevalence rates for high blood pressure and overweight were 18.6 and 12.7%, respectively. Cardiovascular risk factors were more frequent among boys (PR = 1.20; 95%CI = 1.01-1.42). In conclusion, cardiovascular risk factors are a prevalent health issue among students in the city of Londrina.

Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of aortic atherosclerotic thrombi and ulcers.

PubMed

Elsayed, Mahmoud; Bulur, Serkan; Kalla, Aditi; Ahmed, Mustafa I; Hsiung, Ming C; Uygur, Begum; Alagic, Nermina; Sungur, Aylin; Singh, Satinder; Nanda, Navin C

2016-08-01

We present two cases in whom live/real time three-dimensional transesophageal echocardiography (3DTEE) provided incremental value in the assessment of atherosclerotic disease in the aorta. In one patient, it identified additional atherosclerotic ulcers as well as thrombi within them which were missed by two-dimensional (2D) TEE. In both cases, the size of the large mobile atherosclerotic plaque was underestimated by 2DTEE as compared with 3DTEE. Furthermore, 3DTEE provided volume quantification of the thrombi and ulcers which is not possible by 2DTEE. The echocardiographic findings of atherosclerotic plaques were confirmed by computed tomography in one patient and by surgery in the other. © 2016, Wiley Periodicals, Inc.

Vertigo and dizziness in adolescents: Risk factors and their population attributable risk

PubMed Central

Albers, Lucia; Straube, Andreas; Gerstl, Lucia; Blum, Bernhard; Langhagen, Thyra; Jahn, Klaus; Heinen, Florian; von Kries, Rüdiger; Landgraf, Mirjam N.

2017-01-01

Objectives To assess potential risk factors for vertigo and dizziness in adolescents and to evaluate their variability by different vertigo types. The role of possible risk factors for vertigo and dizziness in adolescents and their population relevance needs to be addressed in order to design preventive strategies. Study design The study population consisted of 1482 school-children between the age of 12 and 19 years, who were instructed to fill out a questionnaire on different vertigo types and related potential risk factors. The questionnaire specifically asked for any vertigo, spinning vertigo, swaying vertigo, orthostatic dizziness, and unspecified dizziness. Further a wide range of potential risk factors were addressed including gender, stress, muscular pain in the neck and shoulder region, sleep duration, migraine, coffee and alcohol consumption, physical activity and smoking. Results Gender, stress, muscular pain in the neck and shoulder region, sleep duration and migraine were identified as independent risk factors following mutual adjustment: The relative risk was 1.17 [1.10–1.25] for female sex, 1.07 [1.02–1.13] for stress, 1.24 [1.17–1.32] for muscular pain, and 1.09 [1.03–1.14] for migraine. The population attributable risk explained by these risk factors was 26%, with muscular pain, stress, and migraine accounting for 11%, 4%, and 3% respectively. Conclusion Several established risk factors in adults were also identified in adolescents. Risk factors amenable to prevention accounted for 17% of the total population risk. Therefore, interventions targeting these risk factors may be warranted. PMID:29131843

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions.

PubMed

Jo, Javier A; Fang, Qiyin; Papaioannou, Thanassis; Baker, J Dennis; Dorafshar, Amir H; Reil, Todd; Qiao, Jian-Hua; Fishbein, Michael C; Freischlag, Julie A; Marcu, Laura

2006-01-01

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions

NASA Astrophysics Data System (ADS)

Jo, Javier A.; Fang, Qiyin; Papaioannou, Thanassis; Baker, J. Dennis; Dorafshar, Amir; Reil, Todd; Qiao, Jianhua; Fishbein, Michael C.; Freischlag, Julie A.; Marcu, Laura

2006-03-01

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions

PubMed Central

Jo, Javier A.; Fang, Qiyin; Papaioannou, Thanassis; Baker, J. Dennis; Dorafshar, Amir H.; Reil, Todd; Qiao, Jian-Hua; Fishbein, Michael C.; Freischlag, Julie A.; Marcu, Laura

2007-01-01

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability. PMID:16674179

A fluorescence lifetime spectroscopy study of matrix metalloproteinases -2 and -9 in human atherosclerotic plaque

PubMed Central

Phipps, Jennifer E.; Hatami, Nisa; Galis, Zorina S.; Baker, J. Dennis; Fishbein, Michael C.; Marcu, Laura

2011-01-01

Matrix metalloproteinase (MMP) -2 and -9 play important roles in the progression of atherosclerosis. This study aims to determine whether MMP-2 and -9 content in the fibrotic caps of atherosclerotic plaque is correlated with plaque autofluorescence. A time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) system was used to measure the autofluorescence and assess the biochemical composition of human plaques obtained from carotid endarterectomy. Results presented here demonstrate for the first time the ability to characterize the biochemical composition as it relates to MMP-2 and -9 content in the atherosclerotic plaque cap using a label-free imaging technique implemented with a fiberoptic TR-LIFS system. PMID:21770037

Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial.

PubMed

Sharma, Abhinav; Green, Jennifer B; Dunning, Allison; Lokhnygina, Yuliya; Al-Khatib, Sana M; Lopes, Renato D; Buse, John B; Lachin, John M; Van de Werf, Frans; Armstrong, Paul W; Kaufman, Keith D; Standl, Eberhard; Chan, Juliana C N; Distiller, Larry A; Scott, Russell; Peterson, Eric D; Holman, Rury R

2017-12-01

We evaluated the specific causes of death and their associated risk factors in a contemporary cohort of patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study ( n = 14,671), a cardiovascular (CV) safety trial adding sitagliptin versus placebo to usual care in patients with type 2 diabetes and ASCVD (median follow-up 3 years). An independent committee blinded to treatment assignment adjudicated each cause of death. Cox proportional hazards models were used to identify risk factors associated with each outcome. A total of 1,084 deaths were adjudicated as the following: 530 CV (1.2/100 patient-years [PY], 49% of deaths), 338 non-CV (0.77/100 PY, 31% of deaths), and 216 unknown (0.49/100 PY, 20% of deaths). The most common CV death was sudden death ( n = 145, 27% of CV death) followed by acute myocardial infarction (MI)/stroke ( n = 113 [MI n = 48, stroke n = 65], 21% of CV death) and heart failure (HF) ( n = 63, 12% of CV death). The most common non-CV death was malignancy ( n = 154, 46% of non-CV death). The risk of specific CV death subcategories was lower among patients with no baseline history of HF, including sudden death (hazard ratio [HR] 0.4; P = 0.0036), MI/stroke death (HR 0.47; P = 0.049), and HF death (HR 0.29; P = 0.0057). In this analysis of a contemporary cohort of patients with diabetes and ASCVD, sudden death was the most common subcategory of CV death. HF prevention may represent an avenue to reduce the risk of specific CV death subcategories. © 2017 by the American Diabetes Association.

Adolescent Risk Factors for Child Maltreatment

PubMed Central

Matsuda, Mauri; Greenman, Sarah J.; Augustyn, Megan Bears; Henry, Kimberly L.; Smith, Carolyn A.; Ireland, Timothy O.

2014-01-01

We investigate adolescent risk factors, measured at both early and late adolescence, for involvement in child maltreatment during adulthood. Comprehensive assessments of risk factors for maltreatment that use representative samples with longitudinal data are scarce and can inform multilevel prevention. We use data from the Rochester Youth Development Study, a longitudinal study begun in 1988 with a sample of 1,000 seventh and eighth graders. Participants have been interviewed 14 times and, at the last assessment (age 31), 80% were retained. Risk factors represent 10 developmental domains: area characteristics, family background/structure, parent stressors, exposure to family violence, parent-child relationships, education, peer relationships, adolescent stressors, antisocial behaviors, and precocious transitions to adulthood. Maltreatment is measured by substantiated reports from Child Protective Services records. Many individual risk factors (20 at early adolescence and 14 at later adolescence) are significantly, albeit moderately, predictive of maltreatment. Several developmental domains stand out, including family background/structure, education, antisocial behaviors, and precocious transitions. In addition, there is a pronounced impact of cumulative risk on the likelihood of maltreatment. For example, only 3% of the youth with no risk domains in their background at early adolescence were involved in later maltreatment, but for those with risk in 9 developmental domains the rate was 45%. Prevention programs targeting youth at high risk for engaging in maltreatment should begin during early adolescence when risk factors are already at play. These programs need to be comprehensive, capable of addressing the multiple and interwoven nature of risk that is associated with maltreatment. PMID:24075569

Genetic and environmental risk factors for atherosclerosis regulate transcription of phosphatase and actin regulating gene PHACTR1.

PubMed

Reschen, Michael E; Lin, Da; Chalisey, Anil; Soilleux, Elizabeth J; O'Callaghan, Christopher A

2016-07-01

Coronary artery disease (CAD) risk is associated with non-coding genetic variants at the phosphatase and actin regulating protein 1(PHACTR1) gene locus. The PHACTR1 gene encodes an actin-binding protein with phosphatase regulating activity. The mechanism whereby PHACTR1 influences CAD risk is unknown. We hypothesized that PHACTR1 would be expressed in human cell types relevant to CAD and regulated by atherogenic or genetic factors. Using immunohistochemistry, we demonstrate that PHACTR1 protein is expressed strongly in human atherosclerotic plaque macrophages, lipid-laden foam cells, adventitial lymphocytes and endothelial cells. Using a combination of genomic analysis and molecular techniques, we demonstrate that PHACTR1 is expressed as multiple previously uncharacterized transcripts in macrophages, foam cells, lymphocytes and endothelial cells. Immunoblotting confirmed a total absence of PHACTR1 in vascular smooth muscle cells. Real-time quantitative PCR showed that PHACTR1 is regulated by atherogenic and inflammatory stimuli. In aortic endothelial cells, oxLDL and TNF-alpha both upregulated an intermediate length transcript. A short transcript expressed only in immune cells was upregulated in macrophages by oxidized low-density lipoprotein, and oxidized phospholipids but suppressed by lipopolysaccharide or TNF-alpha. In primary human macrophages, we identified a novel expression quantitative trait locus (eQTL) specific for this short transcript, whereby the risk allele at CAD risk SNP rs9349379 is associated with reduced PHACTR1 expression, similar to the effect of an inflammatory stimulus. Our data demonstrate that PHACTR1 is a key atherosclerosis candidate gene since it is regulated by atherogenic stimuli in macrophages and endothelial cells and we identify an effect of the genetic risk variant on PHACTR1 expression in macrophages that is similar to that of an inflammatory stimulus. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights

Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial.

PubMed

Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Hill, Michael D; Jonasson, Jenny; Kasner, Scott E; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

2017-04-01

Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial. SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov, number NCT01994720. Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 [50%] to ticagrelor and 6610 [50%] to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 [95% CI 0·53-0�

Population-Attributable Risk Proportion of Clinical Risk Factors for Breast Cancer.

PubMed

Engmann, Natalie J; Golmakani, Marzieh K; Miglioretti, Diana L; Sprague, Brian L; Kerlikowske, Karla

2017-09-01

Many established breast cancer risk factors are used in clinical risk prediction models, although the proportion of breast cancers explained by these factors is unknown. To determine the population-attributable risk proportion (PARP) for breast cancer associated with clinical breast cancer risk factors among premenopausal and postmenopausal women. Case-control study with 1:10 matching on age, year of risk factor assessment, and Breast Cancer Surveillance Consortium (BCSC) registry. Risk factor data were collected prospectively from January 1, 1996, through October 31, 2012, from BCSC community-based breast imaging facilities. A total of 18 437 women with invasive breast cancer or ductal carcinoma in situ were enrolled as cases and matched to 184 309 women without breast cancer, with a total of 58 146 premenopausal and 144 600 postmenopausal women enrolled in the study. Breast Imaging Reporting and Data System (BI-RADS) breast density (heterogeneously or extremely dense vs scattered fibroglandular densities), first-degree family history of breast cancer, body mass index (>25 vs 18.5-25), history of benign breast biopsy, and nulliparity or age at first birth (≥30 years vs <30 years). Population-attributable risk proportion of breast cancer. Of the 18 437 women with breast cancer, the mean (SD) age was 46.3 (3.7) years among premenopausal women and 61.7 (7.2) years among the postmenopausal women. Overall, 4747 (89.8%) premenopausal and 12 502 (95.1%) postmenopausal women with breast cancer had at least 1 breast cancer risk factor. The combined PARP of all risk factors was 52.7% (95% CI, 49.1%-56.3%) among premenopausal women and 54.7% (95% CI, 46.5%-54.7%) among postmenopausal women. Breast density was the most prevalent risk factor for both premenopausal and postmenopausal women and had the largest effect on the PARP; 39.3% (95% CI, 36.6%-42.0%) of premenopausal and 26.2% (95% CI, 24.4%-28.0%) of postmenopausal breast cancers could potentially be

Alternation of histone and DNA methylation in human atherosclerotic carotid plaques.

PubMed

Greißel, A; Culmes, M; Napieralski, R; Wagner, E; Gebhard, H; Schmitt, M; Zimmermann, A; Eckstein, H-H; Zernecke, A; Pelisek, J

2015-08-01

Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.

Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Sanjay, E-mail: sanjay@louisville.ed; Center for Environmental Genomics and Integrative Biology, University of Louisville, Louisville, KY 40202; Vladykovskaya, Elena N.

2009-11-15

Exposure to arsenic-contaminated water has been shown to be associated with cardiovascular disease, especially atherosclerosis. We examined the effect of arsenic exposure on atherosclerotic lesion formation, lesion composition and nature in ApoE-/- mice. Early post-natal exposure (3-week-old mice exposed to 49 ppm arsenic as NaAsO{sub 2} in drinking water for 7 weeks) increased the atherosclerotic lesion formation by 3- to 5-fold in the aortic valve and the aortic arch, without affecting plasma cholesterol. Exposure to arsenic for 13 weeks (3-week-old mice exposed to 1, 4.9 and 49 ppm arsenic as NaAsO{sub 2} in drinking water) increased the lesion formation andmore » macrophage accumulation in a dose-dependent manner. Temporal studies showed that continuous arsenic exposure significantly exacerbated the lesion formation throughout the aortic tree at 16 and 36 weeks of age. Withdrawal of arsenic for 12 weeks after an initial exposure for 21 weeks (to 3-week-old mice) significantly decreased lesion formation as compared with mice continuously exposed to arsenic. Similarly, adult exposure to 49 ppm arsenic for 24 weeks, starting at 12 weeks of age increased lesion formation by 2- to 3.6-fold in the aortic valve, the aortic arch and the abdominal aorta. Lesions of arsenic-exposed mice displayed a 1.8-fold increase in macrophage accumulation whereas smooth muscle cell and T-lymphocyte contents were not changed. Expression of pro-inflammatory chemokine MCP-1 and cytokine IL-6 and markers of oxidative stress, protein-HNE and protein-MDA adducts were markedly increased in lesions of arsenic-exposed mice. Plasma concentrations of MCP-1, IL-6 and MDA were also significantly elevated in arsenic-exposed mice. These data suggest that arsenic exposure increases oxidative stress, inflammation and atherosclerotic lesion formation.« less

Risk factors for retained placenta.

PubMed

Coviello, Elizabeth M; Grantz, Katherine L; Huang, Chun-Chih; Kelly, Tara E; Landy, Helain J

2015-12-01

Retained placenta complicates 2-3% of vaginal deliveries and is a known cause of postpartum hemorrhage. Treatment includes manual or operative placental extraction, potentially increasing risks of hemorrhage, infections, and prolonged hospital stays. We sought to evaluate risk factors for retained placenta, defined as more than 30 minutes between the delivery of the fetus and placenta, in a large US obstetrical cohort. We included singleton, vaginal deliveries ≥24 weeks (n = 91,291) from the Consortium of Safe Labor from 12 US institutions (2002-2008). Multivariable logistic regression analyses estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) for potential risk factors for retained placenta stratified by parity, adjusting for relevant confounding factors. Characteristics such as stillbirth, maternal age, race, and admission body mass index were examined. Retained placenta complicated 1047 vaginal deliveries (1.12%). Regardless of parity, significant predictors of retained placenta included stillbirth (nulliparous adjusted OR, 5.67; 95% CI, 3.10-10.37; multiparous adjusted OR, 4.56; 95% CI, 2.08-9.94), maternal age ≥30 years, delivery at 24 0/7 to 27 6/7 compared with 34 weeks or later and delivery in a teaching hospital. In nulliparous women, additional risk factors were identified: longer first- or second-stage labor duration, whereas non-Hispanic black compared with non-Hispanic white race was found to be protective. Body mass index was not associated with an increased risk. Multiple risk factors for retained placenta were identified, particularly the strong association with stillbirth. It is plausible that there could be something intrinsic about stillbirth that causes a retained placenta, or perhaps there are shared pathways of certain etiologies of stillbirth and a risk of retained placenta. Copyright © 2015 Elsevier Inc. All rights reserved.

Progranulin expression in advanced human atherosclerotic plaque.

PubMed

Kojima, Yoji; Ono, Koh; Inoue, Katsumi; Takagi, Yasushi; Kikuta, Ken-ichiro; Nishimura, Masaki; Yoshida, Yoshinori; Nakashima, Yasuhiro; Matsumae, Hironobu; Furukawa, Yutaka; Mikuni, Nobuhiro; Nobuyoshi, Masakiyo; Kimura, Takeshi; Kita, Toru; Tanaka, Makoto

2009-09-01

Progranulin (PGRN) is a unique growth factor that plays an important role in cutaneous wound healing. It has an anti-inflammatory effect and promotes cell proliferation. However, when it is degraded to granulin peptides (GRNs) by neutrophil proteases, a pro-inflammatory reaction occurs. Since injury, inflammation and repair are common features in the progression of atherosclerosis, it is conceivable that PGRN plays a role in atherogenesis. Immunohistochemical analysis of human carotid endoatherectomy specimens indicated that vascular smooth muscle cells (vSMCs) in the intima expressed PGRN. Some macrophages in the plaque also expressed PGRN. We assessed the effect of PGRN on a human monocytic leukemia cell line (THP-1) and human aortic smooth muscle cells (HASMCs). PGRN alone had no effect on HASMC or THP-1 proliferation or migration. However, when THP-1 cells were stimulated with MCP-1, the number of migrated cells decreased in a PGRN-dose-dependent manner. TNF-alpha-induced HASMC migration was enhanced only at 10nM of PGRN. Interleukin-8 (IL-8) secretion from HASMCs was reduced by forced expression of PGRN and increased by RNAi-mediated knockdown of PGRN. While exogenous treatment with recombinant PGRN decreased IL-8 secretion, degraded recombinant GRNs increased IL-8 secretion from HASMCs. The expression of PGRN mainly reduces inflammation and its degradation into GRNs enhances inflammation in atherosclerotic plaque and may contribute to the progression of atherosclerosis.

Risk Factors for Internet Gaming Disorder: Psychological Factors and Internet Gaming Characteristics.

PubMed

Rho, Mi Jung; Lee, Hyeseon; Lee, Taek-Ho; Cho, Hyun; Jung, Dong Jin; Kim, Dai-Jin; Choi, In Young

2017-12-27

Background : Understanding the risk factors associated with Internet gaming disorder (IGD) is important to predict and diagnose the condition. The purpose of this study is to identify risk factors that predict IGD based on psychological factors and Internet gaming characteristics; Methods : Online surveys were conducted between 26 November and 26 December 2014. There were 3568 Korean Internet game users among a total of 5003 respondents. We identified 481 IGD gamers and 3087 normal Internet gamers, based on Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria. Logistic regression analysis was applied to identify significant risk factors for IGD; Results : The following eight risk factors were found to be significantly associated with IGD: functional and dysfunctional impulsivity (odds ratio: 1.138), belief self-control (1.034), anxiety (1.086), pursuit of desired appetitive goals (1.105), money spent on gaming (1.005), weekday game time (1.081), offline community meeting attendance (2.060), and game community membership (1.393; p < 0.05 for all eight risk factors); Conclusions : These risk factors allow for the prediction and diagnosis of IGD. In the future, these risk factors could also be used to inform clinical services for IGD diagnosis and treatment.

Relationship Satisfaction and Risk Factors for Suicide.

PubMed

Till, Benedikt; Tran, Ulrich S; Niederkrotenthaler, Thomas

2017-01-01

Previous studies suggest that troubled romantic relationships are associated with higher risk factors for mental health. However, studies examining the role of relationship satisfaction in suicide risk factors are scarce. We investigated differences in risk factors for suicide between individuals with high relationship satisfaction, individuals with low relationship satisfaction, and singles. Furthermore, we explored patterns of experiencing, and dealing with, conflicts in the relationship and examined associations with suicide risk factors. In this cross-sectional study, we assessed relationship status, relationship satisfaction, specific types of relationship conflicts, and suicide risk factors (i.e., suicidal ideation, hopelessness, depression) with questionnaires among 382 individuals in Austria. Risk factors for suicide were higher among singles than among individuals in happy relationships, but highest among those with low relationship satisfaction [corrected]. Participants reporting a high number of unsolved conflicts in their relationship had higher levels of suicidal ideation, hopelessness, and depression than individuals who tend to solve issues with their partner amicably or report no conflicts. Relationship satisfaction and relationship conflicts reflect risk factors for suicide, with higher levels of suicidal ideation, hopelessness, and depression reported by individuals who mentioned unsolved conflicts with their partner and experienced low satisfaction with their relationship.

Risk factors for post-tonsillectomy hemorrhage.

PubMed

Ikoma, Ryo; Sakane, Sayaka; Niwa, Kazutomo; Kanetaka, Sayaka; Kawano, Toshiro; Oridate, Nobuhiko

2014-08-01

The aim of the present study was to investigate the rate of post-tonsillectomy hemorrhage (PTH) in a single institution and to evaluate the clinical risk factors for PTH. We reviewed the records of 692 patients who underwent tonsillectomy (TE) at Yokohama Minami Kyosai Hospital in Japan. PTH grades were grouped into three categories according to the severity of the hemorrhagic episode: (I) minimal hemorrhage that stopped after noninvasive treatment, (II) hemorrhage requiring treatment with local anesthesia, and (III) hemorrhage requiring reoperation under general anesthesia in the operating room. Clinical risk factors such as sex, age (adults vs. children), TE indication, surgeon's skill level, operative time, ligature type, and duration of antibiotic administration for PTH were investigated. Among the 692 patients, 80 (11.6%) showed PTH, with primary and secondary hemorrhage accounting for 1.6% and 10.0%, respectively. A category III PTH was observed in 18 patients; thus, the overall risk of reoperation was 2.6%. The PTH episode most frequently occurred on postoperative days 5 and 6. The frequency of PTH was significantly higher in male patients and in adults (P<0.01, for both factors). Surgeon's skill was also associated with PTH rate. A stepwise multivariate logistic regression revealed that adult age (odds ratio [OR]=18.9) and male gender (OR=3.78) were the clinical risk factors for PTH. It also revealed that male gender (OR=82065335), adult age (OR=10.6), and surgeon's skill level (OR=7.50) were the clinical risk factors for the category III PTH. The risk of PTH was higher in this report compared with previous reports, which may be associated with the definition of PTH. Clinical risk factors for PTH were adult age and male gender. The surgeon's skill level was an additional risk factor for category III PTH. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Indocyanine Green Enables Near-Infrared Fluorescence Imaging of Lipid-Rich, Inflamed Atherosclerotic Plaques

PubMed Central

Vinegoni, Claudio; Botnaru, Ion; Aikawa, Elena; Calfon, Marcella A.; Iwamoto, Yoshiko; Folco, Eduardo J.; Ntziachristos, Vasilis; Weissleder, Ralph; Libby, Peter; Jaffer, Farouc A.

2011-01-01

New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. While molecular imaging agents are available for lower-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries [AU: ok? YES]. Here, we have demonstrated that indocyanine green (ICG), an FDA-approved near-infrared fluorescence (NIRF) emitting compound, targets atheromas within 20 minutes of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aortae, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging studies showed high plaque target-to-background ratios in atheroma-bearing rabbits injected with ICG, compared to atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans. PMID:21613624

SRXRF Study of Chemical Elements Content in the Atherosclerotic Plaque of Heart Vessels

NASA Astrophysics Data System (ADS)

Zhuravskaya, E. Ya.; Savchenko, T. I.; Chankina, O. V.; Polonskaya, Ya. V.; Chernyavskii, A. M.; Ragino, Yu. I.; Shcherbakova, L. V.

The SRXRF method has made it possible, for the first time, to determine the multielement composition in the atherosclerotic substrates of heart vessels after surgical interventions. The main advantage of the method is the possibility to analyze small samples without their destruction. As the amount of material to test is insufficient, we have developed a special technique for sample preparation. The concentrations of K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, Br, Sr, Zr, and Pb were measured in stable and unstable plaques. In all the samples studied, Ca is dominating, particularly, in the unstable plaque. No reliable difference was established for other elements measured. A high degree of the association of Ca with Fe, Zn and Sr has been revealed in the atherosclerotic plaques. Measurements were performed using SR from the VEPP-3 storage ring.

Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

PubMed Central

Di Pietro, Marisa; Filardo, Simone; De Santis, Fiorenzo; Sessa, Rosa

2013-01-01

Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development. PMID:23877837

Renal Artery Stenting in Patients With Documented Resistant Hypertension and Atherosclerotic Renal Artery Stenosis (ANDORRA)

ClinicalTrials.gov

2018-01-24

Hypertension; Hypertension Resistant to Conventional Therapy; Angiographically Proven Grade III Unilateral or Bilateral Atherosclerotic Renal Artery Stenosis (ARAS) Greater Than or Equal to 60 Percent

[Risk factors of necrotizing enterocolitis].

PubMed

Tapia-Rombo, C A; Velasco-Lavín, M R; Nieto-Caldelas, A

1993-09-01

The purpose of the present study is to compare risk factors of necrotizing enterocolitis (NEC) between two group: group A, newborns with the disease and group B, newborns with other diseases different from NEC, in order to know if these risk factors are more frequent or not in the first group. We assessed the clinical records of all the patients hospitalized in the Neonatal Intensive Care Unit and Neonatology Service of the La Raza General Hospital between 1987 and 1991 with the diagnosis of NEC. They were compared with 65 clinical records chosen at random of patients hospitalized in the same Unit with other diagnosis at the same time, and who were discharged by improvement or deceased. In all of them were look for known risk factors for NEC generally accepted such as: prematurity, neonatal asphyxia, poliglobulia, cyanotic congenital heart disease, patent ductus arteriosus, respiratory distress syndrome, catheterization of umbilical vessels, early feeding of elevated formula increases, exchange exchange transfusion, hypoxic ischemic encephalopathy, infection, etc. Just 25 records of the possible 50 with the diagnosis of NEC full filled inclusion criteria. There were no statistically significant difference in weight, sex, mortality and known risk factors of NEC between both groups. Were concluded that NEC is a disease of unknown etiology that should be studied more thoroughly. The known risk factors must be avoided because the patient susceptibility probably play an important role.

Configurations of Common Childhood Psychosocial Risk Factors

ERIC Educational Resources Information Center

Copeland, William; Shanahan, Lilly; Costello, E. Jane; Angold, Adrian

2009-01-01

Background: Co-occurrence of psychosocial risk factors is commonplace, but little is known about psychiatrically-predictive configurations of psychosocial risk factors. Methods: Latent class analysis (LCA) was applied to 17 putative psychosocial risk factors in a representative population sample of 920 children ages 9 to 17. The resultant class…

Effects of Smad decoy ODN on shear stress-induced atherosclerotic ApoE-/-mouse

PubMed Central

An, Hyun-Jin; Lee, Woo-Ram; Kim, Kyung-Hyun; Kim, Jung-Yeon; Kim, Woon-Hae; Park, Kwan-Kyu; Youn, Sung Won

2015-01-01

Atherosclerosis is a complex disease which involves both genetic and environmental factors in its development and progression. Shear stress is the drag force per unit area acting on the endothelium as a result of blood flow, and it plays a critical role in plaque location and progression. TGF-β1 is often regarded to have pro-atherosclerotic effect on vascular disease. TGF-β1 downstream targets Smad, for regulating a set of genes associated with atherosclerosis. Therefore, modulation of TGF-β1 and Smad expression may be the important targets for the prevention and treatment of shear stress-induced vascular disease. However, the precise mechanism of the anti-atherosclerotic effects of novel therapeutic approach has not been elucidated by using animal models regarding the shear stress-induced vascular disease. Therefore, we designed to test whether Smad decoy ODN would prevent the development of atherosclerosis in the shear stress-induced ApoE-/-mice on a western diet. We examined the effect of cast placement on the development of atherosclerosis, and the carotid artery was harvested at the sacrifice to observe histological changes. Also, we evaluated the impact of Smad decoy ODN in the regulation of genes expression related to atherosclerosis, including TGF-β1, PAI-1, and α-SMA. Our results showed that western diet with cast placement developed atherosclerosis in ApoE-/-mouse. Also, administration of Smad decoy ODN decreases the expression of TGF-β1, PAI-1, and α-SMA. These results demonstrate the potential of Smad decoy ODN to prevent the progression of atherosclerosis in ApoE-/-mouse model with western diet and shear stress. PMID:26097583

Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques contralateral to symptomatic carotid stenosis: an ultra small superparamagnetic iron oxide enhanced magnetic resonance study

PubMed Central

Tang, Tjun Y; Howarth, Simon P S; Miller, Sam R; Graves, Martin J; U‐King‐Im, Jean‐Marie; Trivedi, Rikin A; Li, Zhi Yong; Walsh, Stewart R; Brown, Andrew P; Kirkpatrick, Peter J; Gaunt, Michael E; Gillard, Jonathan H

2007-01-01

Background Inflammation is a recognised risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of magnetic resonance (MR) defined inflammation using ultra small superparamagnetic iron oxide (USPIO) particles within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis contralateral to the symptomatic side. Methods 20 symptomatic patients with contralateral disease and 20 completely asymptomatic patients underwent multi‐sequence MR imaging before and 36 h after USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change was compared across all quadrants in the two groups. Results The mean percentage of quadrants showing signal loss was 53% in the contralateral group compared with 31% in completely asymptomatic individuals (p = 0.025). The mean percentages showing enhancement were 44% and 65%, respectively (p = 0.024). The mean signal difference between the two groups was 8.6% (95% CI 1.6% to 15.6%; p = 0.017). Conclusions Truly asymptomatic plaques seem to demonstrate inflammation but not to the extent of the contralateral asymptomatic stenosis to the symptomatic side. Inflammatory activity may be a significant risk factor in asymptomatic disease. PMID:17578854

Skin Cancer: Biology, Risk Factors & Treatment

MedlinePlus

... turn Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer 2013 Table ... Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma ...

Managing Multiple Risk Factors.

DTIC Science & Technology

1998-09-01

to the racial differences in cardiovascular risk and events among women. High levels of socioeconomic stress, higher dietary fat intake and sedentary ... lifestyle are more prevalent among black than white women. The proposed study will address the issue of whether the cluster of risk factors for

Non-dietary environmental risk factors in prostate cancer

PubMed Central

Ferrís-i-Tortajada, J; Berbel-Tornero, O; Garcia-i-Castell, J; López-Andreu, J.A.; Sobrino-Najul, E; Ortega-García, J.A.

2016-01-01

Introduction The aim is to update and disclose the main environmental risk factors, excluding dietary factors, involved in the etiopathology of prostate cancer. Materials and methods Bibliographic review of the last 25 years of non-dietary environmental risk factors associated with prostate cancer between 1985 and 2010, obtained from MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Environmental Risk Factors/Tobacco/Infectious-Inflammatory Factors/Pesticides/Vasectomy/Occupational Exposures/ Chemoprevention Agents/Radiation and Prostate Cancer. Results While some non-dietary environmental risk factors increase the risk of acquiring the disease, others decrease it. Of the former, it is worth mentioning exposal to tobacco smoke, chronic infectious-inflammatory prostatic processes and occupational exposure to cadmium, herbicides and pesticides. The first factors that reduce the risk are the use of chemopreventive drugs (Finasterida, Dutasteride) and exposure to ultraviolet solar radiation. With the current data, a vasectomy does not influence the risk of developing the disease. Conclusions The slow process of prostate carcinogenesis is the final result of the interaction of constitutional risk and environmental factors. Non-dietary environmental factors play an important role in the etiopathology of this disease. To appropriately assess the risk factors, extensive case studies that include all the possible variables must be analyzed. PMID:21439685

Positron emission tomography of the vulnerable atherosclerotic plaque in man – a contemporary review

PubMed Central

Pedersen, Sune F; Hag, Anne Mette F; Klausen, Thomas L; Ripa, Rasmus S; Bodholdt, Rasmus P; Kjær, Andreas

2014-01-01

Atherosclerosis is the primary underlying cause of cardiovascular disease (CVD). It is the leading cause of morbidity and mortality in the Western world today and is set to become the prevailing disease and major cause of death worldwide by 2020. In the 1950s surgical intervention was introduced to treat symptomatic patients with high-grade carotid artery stenosis due to atherosclerosis – a procedure known as carotid endarterectomy (CEA). By removing the atherosclerotic plaque from the affected carotid artery of these patients, CEA is beneficial by preventing subsequent ipsilateral ischemic stroke. However, it is known that patients with low to intermediate artery stenosis may still experience ischemic events, leading clinicians to consider plaque composition as an important feature of atherosclerosis. Today molecular imaging can be used for characterization, visualization and quantification of cellular and subcellular physiological processes as they take place in vivo; using this technology we can obtain valuable information on atherosclerostic plaque composition. Applying molecular imaging clinically to atherosclerotic disease therefore has the potential to identify atherosclerotic plaques vulnerable to rupture. This could prove to be an important tool for the selection of patients for CEA surgery in a health system increasingly focused on individualized treatment. This review focuses on current advances and future developments of in vivo atherosclerosis PET imaging in man. PMID:24289282

Automated tissue characterization of in vivo atherosclerotic plaques by intravascular optical coherence tomography images

PubMed Central

Ughi, Giovanni Jacopo; Adriaenssens, Tom; Sinnaeve, Peter; Desmet, Walter; D’hooge, Jan

2013-01-01

Intravascular optical coherence tomography (IVOCT) is rapidly becoming the method of choice for the in vivo investigation of coronary artery disease. While IVOCT visualizes atherosclerotic plaques with a resolution <20µm, image analysis in terms of tissue composition is currently performed by a time-consuming manual procedure based on the qualitative interpretation of image features. We illustrate an algorithm for the automated and systematic characterization of IVOCT atherosclerotic tissue. The proposed method consists in a supervised classification of image pixels according to textural features combined with the estimated value of the optical attenuation coefficient. IVOCT images of 64 plaques, from 49 in vivo IVOCT data sets, constituted the algorithm’s training and testing data sets. Validation was obtained by comparing automated analysis results to the manual assessment of atherosclerotic plaques. An overall pixel-wise accuracy of 81.5% with a classification feasibility of 76.5% and per-class accuracy of 89.5%, 72.1% and 79.5% for fibrotic, calcified and lipid-rich tissue respectively, was found. Moreover, measured optical properties were in agreement with previous results reported in literature. As such, an algorithm for automated tissue characterization was developed and validated using in vivo human data, suggesting that it can be applied to clinical IVOCT data. This might be an important step towards the integration of IVOCT in cardiovascular research and routine clinical practice. PMID:23847728

Global risk factor rankings: the importance of age-based health loss inequities caused by alcohol and other risk factors.

PubMed

Shield, Kevin D; Rehm, Jürgen

2015-06-09

Achieving health equity is a priority of the World Health Organization; however, there is a scant amount of literature on this topic. As the underlying influences that determine health loss caused by risk factors are age-dependent, the aim of this paper is to examine how the risk factor rankings for health loss differ by age. Rankings were based on data obtained from the 2010 Global Burden of Disease study. Health loss (as measured by Disability Adjusted Life Years lost) by risk factor was estimated using Population-Attributable Fractions, years of life lost due to premature mortality, and years lived with disability, which were calculated for 187 countries, 20 age groups and both sexes. Uncertainties of the risk factor rankings were estimated using 1,000 simulations taken from posterior distributions The top risk factors by age were: household air pollution for neonates 0-6 days of age [95% uncertainty interval (UI): 1 to 1]; suboptimal breast feeding for children 7-27 days of age (95% UI: 1-1); childhood underweight for children 28 days to less than 1 year of age and 1-4 years of age (95% UI: 1-2 and 1-1, respectively); iron deficiency for children and youth 5-14 years of age (95% UI: 1-1); alcohol use for people 15-49 years of age (95% UI: 1-2); and dietary risks for people 50 years of age and older (95% UI: 1-1). Rankings of risk factors varied by sex among the older age groups. Alcohol and smoking were the most important risk factors among men 15 years of age and older, and high body mass and intimate partner violence were some of the most important risk factors among women 15 years of age and older. Our analyses confirm that the relative importance of risk factors is age-dependent. Therefore, preventing harms caused by various modifiable risk factors using interventions that target people of different ages should be a priority, especially since easily implemented and cost-effective public health interventions exist.

Suicide in developing countries (2): risk factors.

PubMed

Vijayakumar, Lakshmi; John, Sujit; Pirkis, Jane; Whiteford, Harvey

2005-01-01

The majority of studies on risk factors for suicide have been conducted in developed countries, and less work has been done to systematically profile risk factors in developing countries. The current paper presents a selective review of sociodemographic, clinical, and environmental/situational risk factors in developing countries. Taken together, the evidence suggests that the profiles of risk factors in developing countries demonstrate some differences from those in developed countries. In some developing countries, at least, being female, living in a rural area, and holding religious beliefs that sanction suicide may be of more relevance to suicide risk than these factors are in developed countries. Conversely, being single or having a history of mental illness may be of less relevance. Risk factors that appear to be universal include youth or old age, low socioeconomic standing, substance use, and previous suicide attempts. Recent stressful life events play a role in both developing and developed countries, although their nature may differ (e.g., social change may have more of an influence in the former). Likewise, access to means heightens risk in both, but the specific means may vary (e.g., access to pesticides is of more relevance in developing countries). These findings have clear implications for suicide prevention, suggesting that preventive efforts that have shown promise in developed countries may need to be tailored differently to address the risk factor profile of developing countries.

Risk Factors for Internet Gaming Disorder: Psychological Factors and Internet Gaming Characteristics

PubMed Central

Lee, Hyeseon; Lee, Taek-Ho; Cho, Hyun; Kim, Dai-Jin; Choi, In Young

2017-01-01

Background: Understanding the risk factors associated with Internet gaming disorder (IGD) is important to predict and diagnose the condition. The purpose of this study is to identify risk factors that predict IGD based on psychological factors and Internet gaming characteristics; Methods: Online surveys were conducted between 26 November and 26 December 2014. There were 3568 Korean Internet game users among a total of 5003 respondents. We identified 481 IGD gamers and 3087 normal Internet gamers, based on Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria. Logistic regression analysis was applied to identify significant risk factors for IGD; Results: The following eight risk factors were found to be significantly associated with IGD: functional and dysfunctional impulsivity (odds ratio: 1.138), belief self-control (1.034), anxiety (1.086), pursuit of desired appetitive goals (1.105), money spent on gaming (1.005), weekday game time (1.081), offline community meeting attendance (2.060), and game community membership (1.393; p < 0.05 for all eight risk factors); Conclusions: These risk factors allow for the prediction and diagnosis of IGD. In the future, these risk factors could also be used to inform clinical services for IGD diagnosis and treatment. PMID:29280953

Anti-atherosclerotic effects of pravastatin in brachiocephalic artery in comparison with en face aorta and aortic roots in ApoE/LDLR-/- mice.

PubMed

Kostogrys, Renata B; Franczyk-Zarow, Magdalena; Gasior-Glogowska, Marlena; Kus, Edyta; Jasztal, Agnieszka; Wrobel, Tomasz P; Baranska, Malgorzata; Czyzynska-Cichon, Izabela; Drahun, Anna; Manterys, Angelika; Chlopicki, Stefan

2017-02-01

Cholesterol-dependent and independent mechanisms were proposed to explain anti-atherosclerotic action of statins in humans. However, their effects in murine models of atherosclerosis have not been consistently demonstrated. Here, we studied the effects of pravastatin on atherosclerosis in ApoE/LDLR -/- mice fed a control and atherogenic diet. ApoE/LDLR -/- mice were fed a control (CHOW) or an atherogenic (Low Carbohydrate High Protein, LCHP) diet. Two doses of pravastatin (40mg/kg and 100mg/kg) were used. The anti-atherosclerotic effects of pravastatin in en face aorta, cross-sections of aortic roots and brachiocephalic artery (BCA) were analysed. The lipid profile was determined. Fourier Transform Infrared Spectroscopy followed by Fuzzy C-Means (FCM) clustering was used for the quantitative assessment of plaque composition. Treatment with pravastatin (100mg/kg) decreased total and LDL cholesterol only in the LCHP group, but displayed a pronounced anti-atherosclerotic effect in BCA and abdominal aorta. The anti-atherosclerotic effect of pravastatin (100mg/kg) in BCA was associated with significant alterations of the chemical plaque composition, including a fall in cholesterol and cholesterol esters contents independently on total cholesterol and LDL concentration in plasma. Pravastatin at high (100mg/kg), but not low dose displayed a pronounced anti-atherosclerotic effect in ApoE/LDLR -/- mice fed a CHOW or LCHP diet that was remarkable in BCA, visible in en face aorta, whereas it was not observed in aortic roots, suggesting that previous inconsistencies might have been due to the various sites of atherosclerotic plaque analysis. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

A fluorescence lifetime spectroscopy study of matrix metalloproteinases-2 and -9 in human atherosclerotic plaque.

PubMed

Phipps, Jennifer E; Hatami, Nisa; Galis, Zorina S; Baker, J Dennis; Fishbein, Michael C; Marcu, Laura

2011-09-01

Matrix metalloproteinase (MMP)-2 and -9 play important roles in the progression of atherosclerosis. This study aims to determine whether MMP-2 and -9 content in the fibrotic caps of atherosclerotic plaque is correlated with plaque autofluorescence. A time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) system was used to measure the autofluorescence and assess the biochemical composition of human plaques obtained from carotid endarterectomy. Results presented here demonstrate for the first time the ability to characterize the biochemical composition as it relates to MMP-2 and -9 content in the atherosclerotic plaque cap using a label-free imaging technique implemented with a fiberoptic TR-LIFS system. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

TRAF3IP2 mediates atherosclerotic plaque development and vulnerability in ApoE−/− mice

PubMed Central

Prasad, Sakamuri Siva Sankara Vara; Higashi, Yusuke; Sukhanov, Sergiy; Siddesha, Jalahalli M; Delafontaine, Patrice; Siebenlist, Ulrich; Chandrasekar, Bysani

2016-01-01

Background and aims Atherosclerosis is a major cause of heart attack and stroke. Inflammation plays a critical role in the development of atherosclerosis. Since the cytoplasmic adaptor molecule TRAF3IP2 (TRAF3-Interacting Protein 2) plays a causal role in various autoimmune and inflammatory diseases, we hypothesized that TRAF3IP2 mediates atherosclerotic plaque development. Methods TRAF3IP2/ApoE double knockout (DKO) mice were generated by crossing TRAF3IP2−/− and ApoE−/− mice. ApoE−/− mice served as controls. Both DKO and control mice were fed a high-fat diet for 12 weeks. Plasma lipids were measured by ELISA, atherosclerosis by en face analysis of aorta and plaque cross-section measurements at the aortic valve region, plaque necrotic core area, collagen and smooth muscle cell content by histomorphometry, and aortic gene expression by RT-qPCR. Results The plasma lipoprotein profile was not altered by TRAF3IP2 gene deletion in ApoE−/− mice. While total aortic plaque area was decreased in DKO female, but not male mice, the plaque necrotic area was significantly decreased in DKO mice of both genders. Plaque collagen and smooth muscle cell contents were increased significantly in both female and male DKO mice compared to respective controls. Aortic expression of proinflammatory cytokine (Tumor necrosis factor α, TNFα), chemokine (Chemokine (C-X-C motif) Ligand 1, CXCL1) and adhesion molecule (Vascular cell adhesion molecule 1, VCAM1; and Intercellular adhesion molecule 1, ICAM1) gene expression were decreased in both male and female DKO mice. In addition, the male DKO mice showed a markedly reduced expression of extracellular matrix (ECM)-related genes, including TIMP1 (Tissue inhibitor of metalloproteinase 1), RECK (Reversion-Inducing- Cysteine-Rich Protein with Kazal Motifs) and ADAM17 (A Disintegrin And Metalloproteinase 17). Conclusions TRAF3IP2 plays a causal role in atherosclerotic plaque development and vulnerability, possibly by inducing the

Risk factors for pulmonary tuberculosis in Estonia.

PubMed

Tekkel, M; Rahu, M; Loit, H M; Baburin, A

2002-10-01

To determine the risk factors for pulmonary tuberculosis incidence in Estonia. In a case-control study, the cases were 248 adult tuberculosis patients treated in a hospital in Tallinn between January 1999 and June 2000, and the controls were 248 persons sampled from the Population Registry and matched to cases by sex, year of birth and county of residence. A questionnaire was administered to collect information on potential risk factors. Logistic regression was used to calculate odds ratios and 95% confidence intervals. The main risk factors for tuberculosis were marital status other than married, educational level less than higher, low income, having been in prison, not having own place of residence, current unemployment, current smoking, alcohol consumption, shortage of food, and contact with tuberculosis patients. Place of birth was not a risk factor. Risk of tuberculosis decreased for overweight persons whose individual economic situation had improved during the last year. The pattern of risk factors for pulmonary tuberculosis in Estonia was somewhat different from that in Western European countries; a large percentage of the patients were men, but were not elderly, and immigration and drug abuse did not increase the risk. Major risk factors were related to poverty and low socio-economic status.

Hidden Risk Factors for Women

MedlinePlus

... risk factors are present. History of Preeclampsia/Eclampsia: Women with a history of preeclampsia/eclampsia have an increased risk of ... can increase the risk of stroke. Clotting disorders: Women who’ve ... can include previous history of clots in the legs (deep vein thrombosis) ...

C-reactive protein distribution and correlation with traditional cardiovascular risk factors in the Italian population.

PubMed

Casula, Manuela; Tragni, Elena; Zambon, Antonella; Filippi, Alessandro; Brignoli, Ovidio; Cricelli, Claudio; Poli, Andrea; Catapano, Alberico L

2013-03-01

C-reactive protein (CRP) increases during an inflammatory response; its plasma levels are believed to be an independent predictor of future atherosclerotic disease. We report the distribution of plasma levels of CRP and its possible relationship with other cardiovascular risk factors in an Italian cohort. CRP was assessed in frozen plasma samples of 1949 participants in the CHECK study (2001-2005), which collected clinical and biochemical data from randomly selected subjects (40-79 years) in the setting of Italian general practice. Median CRP (interquartile range) was higher in women (1.42 [0.58-2.86] vs 1.28 [0.58-2.50]; p=.163), in people aged ≥ 65 years (1.74 [0.89-3.34] vs 1.11 [0.52-2.45]; p<.001), in patients with obesity (2.37 [1.27-4.15] vs 1.16 [0.52-2.41]; p<.001), metabolic syndrome (2.12 [1.16-3.72] vs 1.10 [0.50-2.38]; p<.001), or higher cardiovascular risk (2.03 [1.01-3.42] vs 1.19 [0.53-2.50]; p<.001). Stepwise regression analysis showed significant associations (R(2)=.264) of circulating log(e)CRP with body mass index, fibrinogen, apoB, age, gender, smoking habits, physical inactivity, creatinine levels, and systolic blood pressure. This study provides epidemiological data of CRP in the Italian population and reinforces the existing evidences about the close correlation between CRP and markers of inflammation and adiposity. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Opening a New Lipid “Apo-thecary”: Incorporating Apolipoproteins as Potential Risk Factors and Treatment Targets to Reduce Cardiovascular Risk

PubMed Central

Jacobson, Terry A.

2011-01-01

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) represent the cornerstone of drug therapy to reduce low-density lipoprotein (LDL) cholesterol and cardiovascular risk. However, even optimal statin management of LDL cholesterol leaves many patients with residual cardiovascular risk, in part because statins are more effective in reducing LDL cholesterol than apolipoprotein B (Apo B). Apo B may be a better marker of atherogenic risk than LDL cholesterol because Apo B measures the total number of all atherogenic particles (total atherosclerotic burden), including LDL, very low-density lipoprotein, intermediate-density lipoprotein, remnant lipoproteins, and lipoprotein(a). To determine whether Apo B is a better indicator of baseline cardiovascular risk and residual risk after lipid therapy compared with LDL cholesterol, a MEDLINE search of the literature published in English from January 1, 1975, through December 1, 2010, was conducted. On the basis of data from most population studies, elevated Apo B was more strongly associated with incident coronary heart disease than similarly elevated LDL cholesterol. Apo B was also a superior benchmark (vs LDL cholesterol) of statins' cardioprotective efficacy in both primary-prevention and secondary-prevention trials. To minimize cardiovascular risk among persons with hypercholesterolemia or dyslipidemia, the best available evidence suggests that intensive therapy with statins should be initiated to achieve the lowest possible Apo B level (with adequate drug toleration) and then other therapies (eg, niacin, bile acid resins, ezetimibe) added to potentiate these Apo B–lowering effects. In future consensus lipid-lowering treatment guidelines, Apo B should be considered as an index of residual risk, a potential parameter of treatment efficacy, and a treatment target to minimize risk of coronary heart disease. PMID:21803958

Sexual harassment: identifying risk factors.

PubMed

O'Hare, E A; O'Donohue, W

1998-12-01

A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.

Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins.

PubMed

Zhang, Wenli; He, Hongliang; Liu, Jianping; Wang, Ji; Zhang, Suyang; Zhang, Shuangshuang; Wu, Zimei

2013-01-01

High density lipoproteins (HDL) have been successfully reconstructed to deliver a large number of lipophilic drugs. Here, discoidal and spherical recombinant HDL loaded with cardiovascular drug tanshinone IIA (TA) were constructed (TA-d-rHDL and TA-s-rHDL), respectively. And next their in vitro physiochemical and biomimetic properties were characterized. Furthermore, pharmacokinetics, atherosclerotic lesions targeting effects and antiatherogenic efficacies were elaborately performed and compared in atherosclerotic New Zealand White (NZW) rabbits. In vitro characterizations results showed that both TA-d-rHDL and TA-s-rHDL had nano-size diameter, high entrapment efficiency (EE) and drug-loading capacity (DL). Additionally, similar to their native counterparts, TA-d-rHDL maintained remodeling behaviors induced by lecithin cholesterol acyltransferase (LCAT), and TA leaked during remodeling behaviors. Pharmacokinetic studies manifested that both TA-d-rHDL and TA-s-rHDL markedly improved pharmacokinetic behaviors of TA in vivo. Ex vivo imaging demonstrated that both d-rHDL and s-rHDL bound more avidly to atherosclerotic lesions than to normal vessel walls, and s-rHDL had better targeting effect than d-rHDL. Pharmacodynamic tests illustrated that both TA-d-rHDL and TA-s-rHDL had much stronger antiatherogenic efficacies than conventional TA nanostructured lipid carriers (TA-NLC), TA liposomes (TA-L) and commercially available preparation Sulfotanshinone Sodium Injection (SSI). Moreover, TA-s-rHDL had more potent antiatherogenic efficacies than TA-d-rHDL. Collectively our studies indicated that rHDL could be exploited as potential delivery vehicles of TA targeting atherosclerotic lesions as well as synergistically improving efficacies, especially for s-rHDL. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Pathological gambling: risk factors].

PubMed

Bouju, G; Grall-Bronnec, M; Landreat-Guillou, M; Venisse, J-L

2011-09-01

In France, consumption of gambling games increased by 148% between 1960 and 2005. In 2004, gamblers lost approximately 0.9% of household income, compared to 0.4% in 1960. This represents approximately 134 Euros per year and per head. In spite of this important increase, the level remains lower than the European average (1%). However, gambling practices may continue to escalate in France in the next few years, particularly with the recent announce of the legalisation of online games and sports betting. With the spread of legalised gambling, pathological gambling rates may increase in France in the next years, in response to more widely available and more attractive gambling opportunities. In this context, there is a need for better understanding of the risk factors that are implicated in the development and maintenance of pathological gambling. This paper briefly describes the major risk factors for pathological gambling by examining the recent published literature available during the first quarter of 2008. This documentary basis was collected by Inserm for the collective expert report procedure on Gambling (contexts and addictions). Seventy-two articles focusing on risk factors for pathological gambling were considered in this review. Only 47 of them were taken into account for analysis. The selection of these 47 publications was based on the guide on literature analysis established by the French National Agency for Accreditation and Assessment in Health (ANAES, 2000). Some publications from more recent literature have also been added, mostly about Internet gambling. We identify three major types of risk factors implicated in gambling problems: some of them are related to the subject (individual factors), others are related to the object of the addiction, here the gambling activity by itself (structural factors), and the last are related to environment (contextual or situational factors). Thus, the development and maintenance of pathological gambling seems to be

Simultaneous two-photon imaging of cerebral oxygenation and capillary blood flow in atherosclerotic mice

NASA Astrophysics Data System (ADS)

Lu, Xuecong; Li, Baoqiang; Moeini, Mohammad; Lesage, Frédéric

2017-02-01

Gradual changes in brain microvasculature and cerebral capillary blood flow occurring with atherosclerosis may significantly contribute to cognition decline due to their role in brain tissue oxygenation. However, previous stud- ies of the relationship between cerebral capillary blood flow and brain tissue oxygenation are limited. This study aimed to investigate vascular and concomitant changes in brain tissue pO2 with atherosclerosis. Experiments in young healthy C57B1/6 mice (n=6 , WT), young atherosclerotic mice (n=6 , ATX Y) and old atherosclerotic mice (n=6 , ATX O) were performed imaging on the left sensory-motor cortex at resting state under urethane (1.5 g/kg) anesthesia using two-photon fluorescence microscopy. The results showed that pO2 around capillaries, correlated with red blood cell (RBC) flux, increased with atherosclerosis.

Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic lesions in mice

PubMed Central

Pont, Isabel; Calatayud-Pascual, Aracely; López-Castellano, Alicia; Albelda, Elena P.; García-España, Enrique; Martí-Bonmatí, Luis; Frias, Juan C.

2018-01-01

Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were divided into several groups to test the efficacy of this anti-angiogenic drug for early treatment of atherosclerotic lesions. Statistical analysis of the lesions revealed a decrease in the lesion size after 5 weeks of treatment. PMID:29338009

Risk factors, health risks, and risk management for aircraft personnel and frequent flyers.

PubMed

Kim, Jeoum Nam; Lee, Byung Mu

2007-01-01

Health risks associated with long periods of time in flight are of concern to astronauts, crew members, and passengers. Many epidemiological studies showed that occupational and frequent flyers may be susceptible to ocular, cardiovascular, neurological, pulmonary, gastrointestinal, sensory, immunological, physiological, and even developmental disorders. In addition, the incidences of cancer and food poisoning are expected to be higher in such individuals. This article reviews health risks and risk factors associated with air travel, and discusses risk management strategies. To reduce adverse health risks, risk factors such as radiation, infection, stress, temperature, pressure, and circadian rhythm need to be avoided or reduced to levels that are as low as technologically achievable to protect flight personnel and passengers.

CXCR6 regulates the recruitment of pro-inflammatory IL-17A-producing T cells into atherosclerotic aortas

PubMed Central

Butcher, Matthew J.; Wu, Chih-I; Waseem, Tayab

2016-01-01

The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A+ cells play a role in this disease. Although elevated number of CD4+ IL-17A+ (Th17) and IL-17A+TCRγδ+ T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL-17A+ T-cell migration to atherosclerotic lesions are unclear. The chemokine receptor CXCR6 is expressed on several T-cell subsets and plays a pro-atherogenic role in atherosclerosis. Here, we used CXCR6-deficient (Cxcr6 GFP/GFP) apolipoprotein E-deficient (Apoe −/−) mice to investigate the involvement of CXCR6 in the recruitment IL-17A+ T cells to atherosclerotic aortas. Flow cytometric analyses revealed reductions in Th17 and IL-17A+TCRγδ+ T cells within aged Cxcr6 GFP/GFP Apoe −/− aortas, in comparison with age-matched Cxcr6 GFP/+ Apoe −/− aortas. Although CXCR6-sufficient IL-17A+ T cells efficiently migrated toward CXCL16, the migration of CXCR6-deficient IL-17A+ T cells was abolished in transwell assays. Importantly, the recruitment of Cxcr6 GFP/GFP Apoe −/− IL-17A+ T cells into the aortas of Apoe −/− recipients was markedly reduced in short-term adoptive transfer experiments. Altogether these results demonstrate an important role of CXCR6 in the regulation of pathological Th17 and IL-17A+TCRγδ+ T-cell recruitment into atherosclerotic lesions. PMID:26614640

CXCR6 regulates the recruitment of pro-inflammatory IL-17A-producing T cells into atherosclerotic aortas.

PubMed

Butcher, Matthew J; Wu, Chih-I; Waseem, Tayab; Galkina, Elena V

2016-05-01

The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A(+) cells play a role in this disease. Although elevated number of CD4(+) IL-17A(+) (Th17) and IL-17A(+)TCRγδ(+) T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL-17A(+) T-cell migration to atherosclerotic lesions are unclear. The chemokine receptor CXCR6 is expressed on several T-cell subsets and plays a pro-atherogenic role in atherosclerosis. Here, we used CXCR6-deficient (Cxcr6 (GFP/GFP) ) apolipoprotein E-deficient (Apoe (-/-) ) mice to investigate the involvement of CXCR6 in the recruitment IL-17A(+) T cells to atherosclerotic aortas. Flow cytometric analyses revealed reductions in Th17 and IL-17A(+)TCRγδ(+) T cells within aged Cxcr6 (GFP/GFP) Apoe (-/-) aortas, in comparison with age-matched Cxcr6 (GFP/+) Apoe (-/-) aortas. Although CXCR6-sufficient IL-17A(+) T cells efficiently migrated toward CXCL16, the migration of CXCR6-deficient IL-17A(+) T cells was abolished in transwell assays. Importantly, the recruitment of Cxcr6 (GFP/GFP) Apoe (-/-) IL-17A(+) T cells into the aortas of Apoe (-/-) recipients was markedly reduced in short-term adoptive transfer experiments. Altogether these results demonstrate an important role of CXCR6 in the regulation of pathological Th17 and IL-17A(+)TCRγδ(+) T-cell recruitment into atherosclerotic lesions. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.